9-20720370-T-G

Position:

• chr9-20720370-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP3 BP6

The NM_001375567.1(FOCAD):​c.133-10T>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,461,174 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000011 (1 hom.)
• Consequence: FOCAD NM_001375567.1 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.9992
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.45

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
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
• BP6: Variant 9-20720370-T-G is Benign according to our data. Variant chr9-20720370-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3043222.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOCAD	NM_001375567.1	c.133-10T>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000338382.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOCAD	ENST00000338382.11	c.133-10T>G		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001375567.1	P1
FOCAD	ENST00000380249.5	c.133-10T>G		splice_polypyrimidine_tract_variant, intron_variant		1		P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1461174 Hom.: 1 Cov.: 32 AF XY: 0.0000110 AC XY: 8 AN XY: 726830

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

FOCAD-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 20, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	23
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.89
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

LitVar

Other links and lift over

dbSNP: rs868300665; hg19: chr9-20720369;