Variant 1-37998996-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001243878.2(FHL3):c.-16T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000431 in 1,614,194 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00033 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00044 ( 8 hom. )

Consequence

FHL3
NM_001243878.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.752

Variant links:

Genes affected

FHL3 (HGNC:3704): (four and a half LIM domains 3) The protein encoded by this gene is a member of a family of proteins containing a four-and-a-half LIM domain, which is a highly conserved double zinc finger motif. The encoded protein has been shown to interact with the cancer developmental regulators SMAD2, SMAD3, and SMAD4, the skeletal muscle myogenesis protein MyoD, and the high-affinity IgE beta chain regulator MZF-1. This protein may be involved in tumor suppression, repression of MyoD expression, and repression of IgE receptor expression. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

FHL3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 1-37998996-A-G is Benign according to our data. Variant chr1-37998996-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2638685.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 50 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHL3	NM_004468.5 link	c.309T>C	p.Ala103Ala	synonymous_variant	Exon 3 of 6	ENST00000373016.4	NP_004459.2	Q13643
FHL3	NM_001243878.2 link	c.-16T>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 5		NP_001230807.1	Q13643Q96C98
FHL3	NM_001243878.2 link	c.-16T>C		5_prime_UTR_variant	Exon 2 of 5		NP_001230807.1	Q13643Q96C98

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FHL3	ENST00000373016.4 link	c.309T>C	p.Ala103Ala	synonymous_variant	Exon 3 of 6	1	NM_004468.5	ENSP00000362107.3		Q13643

Frequencies

GnomAD3 genomes

AF:

0.000328

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00682

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000936

AC:

235

AN:

251174

Hom.:

AF XY:

0.00108

AC XY:

147

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000979

Gnomad SAS exome

AF:

0.00647

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000441

AC:

645

AN:

1461834

Hom.:

Cov.:

AF XY:

0.000587

AC XY:

427

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000680

Gnomad4 SAS exome

AF:

0.00596

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000360

Gnomad4 OTH exome

AF:

0.000927

GnomAD4 genome

AF:

0.000328

AC:

AN:

152360

Hom.:

Cov.:

AF XY:

0.000429

AC XY:

AN XY:

74524

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00683

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000447

Hom.:

Bravo

AF:

0.000215

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FHL3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.0

DANN

Benign

0.33

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