9-20720500-C-T

Position:

• chr9-20720500-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001375567.1(FOCAD):​c.253C>T​(p.Leu85Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOCAD	NM_001375567.1	c.253C>T	p.Leu85Phe	missense_variant	4/44	ENST00000338382.11	NP_001362496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOCAD	ENST00000338382.11	c.253C>T	p.Leu85Phe	missense_variant	4/44	5	NM_001375567.1	ENSP00000344307	P1
FOCAD	ENST00000380249.5	c.253C>T	p.Leu85Phe	missense_variant	6/46	1		ENSP00000369599	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 21, 2024

The c.253C>T (p.L85F) 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 253, causing the leucine (L) at amino acid position 85 to be replaced by a phenylalanine (F). 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	0.22
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Pathogenic	1.0
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.26
Sift	Uncertain	0.0040	D;D
Sift4G	Pathogenic	0.0	D;D
Vest4		0.92
MutPred		0.17		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.49
MPC		0.028
ClinPred		0.98	D
GERP RS		4.6
gMVP		0.63

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: chr9-20720499;