12-52691432-C-T

Variant names:

• chr12-52691432-C-T
• rs1464619211
• NM_175078.3:c.1470G>A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_175078.3(KRT77):​c.1470G>A​(p.Gln490Gln) variant causes a synonymous 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: 33)
• Consequence: KRT77 NM_175078.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682

Genes affected

KRT77 (HGNC:20411): (keratin 77) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene encodes an epithelial keratin that is expressed in the skin and eccrine sweat glands. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=-0.682 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT77	NM_175078.3	c.1470G>A	p.Gln490Gln	synonymous_variant	Exon 9 of 9	ENST00000341809.8	NP_778253.2
KRT77	XM_011538288.3	c.771G>A	p.Gln257Gln	synonymous_variant	Exon 9 of 9		XP_011536590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT77	ENST00000341809.8	c.1470G>A	p.Gln490Gln	synonymous_variant	Exon 9 of 9	1	NM_175078.3	ENSP00000342710.3
KRT77	ENST00000553168.1	n.*808G>A		non_coding_transcript_exon_variant	Exon 10 of 10	1		ENSP00000448207.1
KRT77	ENST00000553168.1	n.*808G>A		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000448207.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	4.3
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs1464619211; hg19: chr12-53085216;