9-20715363-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting

The NM_001375567.1(FOCAD):c.10G>T(p.Asp4Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000102 in 1,371,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

FOCAD
NM_001375567.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.69

Publications

1 publications found

Variant links:

Genes affected

FOCAD (HGNC:23377): (focadhesin) Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

FOCAD Gene-Disease associations (from GenCC):

liver disease, severe congenital
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

FOCAD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13744605).

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.0000102 (14/1371346) while in subpopulation AMR AF = 0.000332 (13/39122). AF 95% confidence interval is 0.000197. There are 0 homozygotes in GnomAdExome4. There are 5 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOCAD	NM_001375567.1 link	c.10G>T	p.Asp4Tyr	missense_variant	Exon 2 of 44	ENST00000338382.11	NP_001362496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOCAD	ENST00000338382.11 link	c.10G>T	p.Asp4Tyr	missense_variant	Exon 2 of 44	5	NM_001375567.1	ENSP00000344307.6		Q5VW36
FOCAD	ENST00000380249.5 link	c.10G>T	p.Asp4Tyr	missense_variant	Exon 4 of 46	1		ENSP00000369599.1		Q5VW36

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000574

AC:

AN:

226628

AF XY:

0.0000324

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000460

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000102

AC:

AN:

1371346

Hom.:

Cov.:

AF XY:

0.00000736

AC XY:

AN XY:

679440

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31268

American (AMR)

AF:

0.000332

AC:

AN:

39122

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23906

East Asian (EAS)

AF:

0.00

AC:

AN:

37026

South Asian (SAS)

AF:

0.0000148

AC:

AN:

67758

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49766

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5476

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1061262

Other (OTH)

AF:

0.00

AC:

AN:

55762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Dec 10, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 4 of the FOCAD protein (p.Asp4Tyr). This variant is present in population databases (rs757339586, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with FOCAD-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.012

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.2

PhyloP100

5.7

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.010

D;D

Vest4

0.47

MutPred

0.23

Gain of MoRF binding (P = 0.0245);Gain of MoRF binding (P = 0.0245);

MVP

0.27

MPC

0.026

ClinPred

0.35

GERP RS

5.8

gMVP

0.57

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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9-20715363-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over