rs61732084

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004468.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHL3	NM_004468.5	MANE Select	c.307G>A	p.Ala103Thr	missense	Exon 3 of 6	NP_004459.2	Q13643
	FHL3	NM_001243878.2		c.-18G>A		5_prime_UTR	Exon 2 of 5	NP_001230807.1	Q96C98

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FHL3	ENST00000373016.4	TSL:1 MANE Select	c.307G>A	p.Ala103Thr	missense	Exon 3 of 6	ENSP00000362107.3	Q13643
FHL3	ENST00000485803.5	TSL:1	n.297G>A		non_coding_transcript_exon	Exon 2 of 5
FHL3	ENST00000850578.1		c.307G>A	p.Ala103Thr	missense	Exon 3 of 6	ENSP00000520866.1	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

GnomAD2 exomes

AF:

0.00420

AC:

1054

AN:

251144

AF XY:

0.00317

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 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

African (AFR)

AF:

0.0581

AC:

1944

AN:

33478

American (AMR)

AF:

0.00259

AC:

116

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.000731

AC:

AN:

39696

South Asian (SAS)

AF:

0.000197

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000692

AC:

AN:

1111960

Other (OTH)

AF:

0.00361

AC:

218

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

136

271

407

542

678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0161

AC:

2446

AN:

152324

Hom.:

Cov.:

AF XY:

0.0153

AC XY:

1143

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0562

AC:

2337

AN:

41562

American (AMR)

AF:

0.00497

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000579

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68030

Other (OTH)

AF:

0.00993

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

116

232

349

465

581

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00587

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

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

PhyloP100

5.0

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

Mutation Taster

=87/13

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over