12-52902133-A-T

Variant names:

• chr12-52902133-A-T
• rs2035875
• NM_002273.4:c.325-61T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002273.4(KRT8):​c.325-61T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 30)
• Consequence: KRT8 NM_002273.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625
• Publications: 15 publications found

Genes affected

KRT8 (HGNC:6446): (keratin 8) This gene is a member of the type II keratin family clustered on the long arm of chromosome 12. Type I and type II keratins heteropolymerize to form intermediate-sized filaments in the cytoplasm of epithelial cells. The product of this gene typically dimerizes with keratin 18 to form an intermediate filament in simple single-layered epithelial cells. This protein plays a role in maintaining cellular structural integrity and also functions in signal transduction and cellular differentiation. Mutations in this gene cause cryptogenic cirrhosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

KRT8 Gene-Disease associations (from GenCC):

• cirrhosis, familial

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002273.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT8	NM_002273.4	MANE Select	c.325-61T>A		intron	N/A	NP_002264.1
	KRT8	NM_001256282.2		c.409-61T>A		intron	N/A	NP_001243211.1
	KRT8	NM_001256293.2		c.325-61T>A		intron	N/A	NP_001243222.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT8	ENST00000692008.1	MANE Select	c.325-61T>A		intron	N/A	ENSP00000509398.1
	KRT8	ENST00000552150.5	TSL:1	c.409-61T>A		intron	N/A	ENSP00000449404.1
	KRT8	ENST00000871797.1		c.325-61T>A		intron	N/A	ENSP00000541856.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 12

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 10450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.81
PhyloP100		-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

Other links and lift over

dbSNP: rs2035875; hg19: chr12-53295917;