9-20715313-T-G

Variant names:

• chr9-20715313-T-G
• rs56301631
• NM_001375567.1:c.-32-9T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001375567.1(FOCAD):​c.-32-9T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000813 in 1,229,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: FOCAD NM_001375567.1 intron
• Scores: Splicing: ADA: 0.9257
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOCAD	NM_001375567.1	c.-32-9T>G		intron_variant	Intron 1 of 43	ENST00000338382.11	NP_001362496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOCAD	ENST00000338382.11	c.-32-9T>G		intron_variant	Intron 1 of 43	5	NM_001375567.1	ENSP00000344307.6
FOCAD	ENST00000380249.5	c.-32-9T>G		intron_variant	Intron 3 of 45	1		ENSP00000369599.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.13e-7 AC: 1 AN: 1229310 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 606838

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27240

American (AMR) AF: 0.00 AC: 0 AN: 29940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21266

East Asian (EAS) AF: 0.00 AC: 0 AN: 34354

South Asian (SAS) AF: 0.00 AC: 0 AN: 53796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4984

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 960996

Other (OTH) AF: 0.00 AC: 0 AN: 50176

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Benign	0.80
PhyloP100		3.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.93
dbscSNV1_RF	Benign	0.71
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

Other links and lift over

dbSNP: rs56301631; hg19: chr9-20715312;