Variant X-136209862-T-TC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 6P and 2B. PVS1_StrongPM2BP6_Moderate

The NM_001159699.2(FHL1):c.737-3dupC variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,170,172 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0000092 ( 0 hom., 1 hem., cov: 20)

Exomes 𝑓: 0.0000028 ( 0 hom. 0 hem. )

Consequence

FHL1
NM_001159699.2 splice_acceptor, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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:

FHL1 (HGNC:):

FHL1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 1.664422 fraction of the gene. Cryptic splice site detected, with MaxEntScore 13, offset of 0 (no position change), new splice context is: tctttttttttcccccccAGggt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant X-136209862-T-TC is Benign according to our data. Variant chrX-136209862-T-TC is described in ClinVar as [Benign]. Clinvar id is 2893227.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHL1	NM_001159702.3 linkuse as main transcript	c.889-3dupC		splice_acceptor_variant, intron_variant		ENST00000394155.8	NP_001153174.1	Q13642-2
FHL1	NM_001159699.2 linkuse as main transcript	c.737-3dupC		splice_acceptor_variant, intron_variant		ENST00000370683.6	NP_001153171.1	Q13642-5

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.00000916

AC:

AN:

109165

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

31681

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000404

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000178

AC:

AN:

168269

Hom.:

AF XY:

0.0000343

AC XY:

AN XY:

58243

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000402

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000283

AC:

AN:

1061007

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

344357

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000245

Gnomad4 OTH exome

AF:

0.0000224

GnomAD4 genome

AF:

0.00000916

AC:

AN:

109165

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

31681

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000404

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

X-linked myopathy with postural muscle atrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

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