X-136209863-C-T

Position:

chrX-136209863-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001159702.3(FHL1):c.889-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 10115 hom., 14664 hem., cov: 20)

Exomes 𝑓: 0.54 ( 106771 hom. 182938 hem. )

Failed GnomAD Quality Control

Consequence

FHL1
NM_001159702.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00007098

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:16

Conservation

PhyloP100: -0.111

Variant links:

Genes affected

FHL1 (HGNC:3702): (four and a half LIM domains 1) This gene encodes a member of the four-and-a-half-LIM-only protein family. Family members contain two highly conserved, tandemly arranged, zinc finger domains with four highly conserved cysteines binding a zinc atom in each zinc finger. Expression of these family members occurs in a cell- and tissue-specific mode and these proteins are involved in many cellular processes. Mutations in this gene have been found in patients with Emery-Dreifuss muscular dystrophy. Multiple alternately spliced transcript variants which encode different protein isoforms have been described.[provided by RefSeq, Nov 2009]

FHL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant X-136209863-C-T is Benign according to our data. Variant chrX-136209863-C-T is described in ClinVar as [Benign]. Clinvar id is 198466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-136209863-C-T is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHL1	NM_001159699.2 linkuse as main transcript	c.737-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000370683.6	NP_001153171.1
FHL1	NM_001159702.3 linkuse as main transcript	c.889-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000394155.8	NP_001153174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHL1	ENST00000370683.6 linkuse as main transcript	c.737-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001159699.2	ENSP00000359717	P1	Q13642-5
FHL1	ENST00000394155.8 linkuse as main transcript	c.889-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001159702.3	ENSP00000377710		Q13642-2

Frequencies

GnomAD3 genomes

AF:

0.502

AC:

53570

AN:

106685

Hom.:

10113

Cov.:

AF XY:

0.495

AC XY:

14644

AN XY:

29593

show subpopulations

Gnomad AFR

AF:

0.384

Gnomad AMI

AF:

0.508

Gnomad AMR

AF:

0.490

Gnomad ASJ

AF:

0.478

Gnomad EAS

AF:

0.695

Gnomad SAS

AF:

0.479

Gnomad FIN

AF:

0.627

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.550

Gnomad OTH

AF:

0.449

GnomAD3 exomes

AF:

0.517

AC:

87246

AN:

168780

Hom.:

15334

AF XY:

0.492

AC XY:

28211

AN XY:

57356

show subpopulations

Gnomad AFR exome

AF:

0.367

Gnomad AMR exome

AF:

0.537

Gnomad ASJ exome

AF:

0.454

Gnomad EAS exome

AF:

0.679

Gnomad SAS exome

AF:

0.445

Gnomad FIN exome

AF:

0.614

Gnomad NFE exome

AF:

0.513

Gnomad OTH exome

AF:

0.496

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.541

AC:

578109

AN:

1069496

Hom.:

106771

Cov.:

AF XY:

0.536

AC XY:

182938

AN XY:

341272

show subpopulations

Gnomad4 AFR exome

AF:

0.376

Gnomad4 AMR exome

AF:

0.539

Gnomad4 ASJ exome

AF:

0.479

Gnomad4 EAS exome

AF:

0.649

Gnomad4 SAS exome

AF:

0.481

Gnomad4 FIN exome

AF:

0.629

Gnomad4 NFE exome

AF:

0.544

Gnomad4 OTH exome

AF:

0.524

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.502

AC:

53581

AN:

106725

Hom.:

10115

Cov.:

AF XY:

0.495

AC XY:

14664

AN XY:

29643

show subpopulations

Gnomad4 AFR

AF:

0.384

Gnomad4 AMR

AF:

0.491

Gnomad4 ASJ

AF:

0.478

Gnomad4 EAS

AF:

0.695

Gnomad4 SAS

AF:

0.479

Gnomad4 FIN

AF:

0.627

Gnomad4 NFE

AF:

0.550

Gnomad4 OTH

AF:

0.452

Alfa

AF:

0.541

Hom.:

9977

Bravo

AF:

0.492

ClinVar

Significance: Benign

Submissions summary: Benign:16

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 29, 2021	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 22, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 05, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

X-linked myopathy with postural muscle atrophy

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

Myopathy, reducing body, X-linked, early-onset, severe

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Uruguay Faciocardiomusculoskeletal syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Myopathy, reducing body, X-linked, childhood-onset

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

X-linked scapuloperoneal muscular dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

X-linked myopathy with postural muscle atrophy;C2678061:X-linked scapuloperoneal muscular dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

May 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.048

DANN

Benign

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000071

dbscSNV1_RF

Benign

0.072

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over