9-20740252-A-G

Position:

• chr9-20740252-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001375567.1(FOCAD):​c.304A>G​(p.Ile102Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FOCAD NM_001375567.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.102410465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOCAD	NM_001375567.1	c.304A>G	p.Ile102Val	missense_variant	5/44	ENST00000338382.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOCAD	ENST00000338382.11	c.304A>G	p.Ile102Val	missense_variant	5/44	5	NM_001375567.1	P1
FOCAD	ENST00000380249.5	c.304A>G	p.Ile102Val	missense_variant	7/46	1		P1
FOCAD	ENST00000604103.1	n.99A>G		non_coding_transcript_exon_variant	2/5	4
FOCAD	ENST00000605031.5	n.80A>G		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452272 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 722368

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 15, 2024

The c.304A>G (p.I102V) alteration is located in exon 7 (coding exon 4) of the FOCAD gene. This alteration results from a A to G substitution at nucleotide position 304, causing the isoleucine (I) at amino acid position 102 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	0.098
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.88
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.54	D
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.68	D;D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.020	N;N
REVEL	Benign	0.053
Sift	Benign	0.40	T;T
Sift4G	Benign	0.29	T;T
Vest4		0.13
MutPred		0.18		Gain of methylation at K103 (P = 0.1239);Gain of methylation at K103 (P = 0.1239);
MVP		0.29
MPC		0.0062
ClinPred		0.19	T
GERP RS		3.3
gMVP		0.20

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: chr9-20740251;