9-20720441-C-T

Variant names:

• chr9-20720441-C-T
• NM_001375567.1:c.194C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001375567.1(FOCAD):​c.194C>T​(p.Ala65Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FOCAD NM_001375567.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.36

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 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.194C>T	p.Ala65Val	missense_variant	Exon 4 of 44	ENST00000338382.11	NP_001362496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOCAD	ENST00000338382.11	c.194C>T	p.Ala65Val	missense_variant	Exon 4 of 44	5	NM_001375567.1	ENSP00000344307.6
FOCAD	ENST00000380249.5	c.194C>T	p.Ala65Val	missense_variant	Exon 6 of 46	1		ENSP00000369599.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Nov 17, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.194C>T (p.A65V) alteration is located in exon 6 (coding exon 3) of the FOCAD gene. This alteration results from a C to T substitution at nucleotide position 194, causing the alanine (A) at amino acid position 65 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Pathogenic	1.0
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.015	D;D
Vest4		0.75
MutPred		0.30		Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP		0.44
MPC		0.025
ClinPred		0.96	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-20720440;