Variant 1-37998998-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004468.5(FHL3):c.307G>A(p.Ala103Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00301 in 1,614,134 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A103A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.016 ( 73 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 63 hom. )

Consequence

FHL3
NM_004468.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.96

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014649272).

BP6

Variant 1-37998998-C-T is Benign according to our data. Variant chr1-37998998-C-T is described in ClinVar as [Benign]. Clinvar id is 783283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHL3	NM_004468.5 link	c.307G>A	p.Ala103Thr	missense_variant	Exon 3 of 6	ENST00000373016.4	NP_004459.2	Q13643
FHL3	NM_001243878.2 link	c.-18G>A		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.307G>A	p.Ala103Thr	missense_variant	Exon 3 of 6	1	NM_004468.5	ENSP00000362107.3		Q13643

Frequencies

GnomAD3 genomes

AF:

0.0160

AC:

2435

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0561

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00420

AC:

1054

AN:

251144

Hom.:

AF XY:

0.00317

AC XY:

430

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.0569

Gnomad AMR exome

AF:

0.00240

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000652

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00165

AC:

2409

AN:

1461810

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

1085

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.0581

Gnomad4 AMR exome

AF:

0.00259

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000731

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000692

Gnomad4 OTH exome

AF:

0.00361

GnomAD4 genome

AF:

0.0161

AC:

2446

AN:

152324

Hom.:

Cov.:

AF XY:

0.0153

AC XY:

1143

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0562

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00302

Hom.:

Bravo

AF:

0.0176

ESP6500AA

AF:

0.0522

AC:

230

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00523

AC:

635

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 20, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.82

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.44

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.46

Sift

Benign

0.073

Sift4G

Benign

0.55

Polyphen

0.99

Vest4

0.60

MVP

0.74

MPC

0.96

ClinPred

0.028

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.068

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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