9-20720318-GGTGT-GGTGTGTGT

Variant names:

• chr9-20720318-G-GGTGT
• rs112284387
• NM_001375567.1:c.133-49_133-46dupGTGT

Variant summary

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

The NM_001375567.1(FOCAD):​c.133-49_133-46dupGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,720 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOCAD NM_001375567.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391
• 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 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.133-49_133-46dupGTGT		intron_variant	Intron 3 of 43	ENST00000338382.11	NP_001362496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOCAD	ENST00000338382.11	c.133-62_133-61insGTGT		intron_variant	Intron 3 of 43	5	NM_001375567.1	ENSP00000344307.6
FOCAD	ENST00000380249.5	c.133-62_133-61insGTGT		intron_variant	Intron 5 of 45	1		ENSP00000369599.1

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151606 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1276770 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 636794

African (AFR) AF: 0.00 AC: 0 AN: 30146

American (AMR) AF: 0.00 AC: 0 AN: 40414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22554

East Asian (EAS) AF: 0.00 AC: 0 AN: 37470

South Asian (SAS) AF: 0.00 AC: 0 AN: 74964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5260

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 961440

Other (OTH) AF: 0.00 AC: 0 AN: 53938

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151720 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74144

African (AFR) AF: 0.00 AC: 0 AN: 41404

American (AMR) AF: 0.0000657 AC: 1 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67854

Other (OTH) AF: 0.00 AC: 0 AN: 2100

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs112284387; hg19: chr9-20720317;