9-20717797-G-A

Variant names:

• chr9-20717797-G-A
• rs752843013
• NM_001375567.1:c.61G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001375567.1(FOCAD):​c.61G>A​(p.Val21Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V21L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FOCAD NM_001375567.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.79
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOCAD	NM_001375567.1	c.61G>A	p.Val21Met	missense_variant	Exon 3 of 44	ENST00000338382.11	NP_001362496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOCAD	ENST00000338382.11	c.61G>A	p.Val21Met	missense_variant	Exon 3 of 44	5	NM_001375567.1	ENSP00000344307.6
FOCAD	ENST00000380249.5	c.61G>A	p.Val21Met	missense_variant	Exon 5 of 46	1		ENSP00000369599.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	0.0027	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.0071	T
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-1.2	T
PhyloP100		4.8
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.0060	D;D
Sift4G	Pathogenic	0.0	D;D
Vest4		0.58
MutPred		0.28		Gain of disorder (P = 0.1454);Gain of disorder (P = 0.1454);
MVP		0.47
MPC		0.026
ClinPred		0.96	D
GERP RS		5.7
gMVP		0.61
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs752843013; hg19: chr9-20717796;