Variant chr12-52691434-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_175078.3(KRT77):c.1468C>A(p.Gln490Lys) variant causes a missense 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. 13/21 in silico tools predict 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)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRT77
NM_175078.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.53

Variant links:

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]

KRT77 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11805007).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT77	NM_175078.3 linkuse as main transcript	c.1468C>A	p.Gln490Lys	missense_variant	9/9	ENST00000341809.8	NP_778253.2	Q7Z794Q0IIN1
KRT77	XM_011538288.3 linkuse as main transcript	c.769C>A	p.Gln257Lys	missense_variant	9/9		XP_011536590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KRT77	ENST00000341809.8 linkuse as main transcript	c.1468C>A	p.Gln490Lys	missense_variant	9/9	1	NM_175078.3	ENSP00000342710.3	Q7Z794
KRT77	ENST00000553168.1 linkuse as main transcript	n.*806C>A		non_coding_transcript_exon_variant	10/10	1		ENSP00000448207.1	F8VS61
KRT77	ENST00000553168.1 linkuse as main transcript	n.*806C>A		3_prime_UTR_variant	10/10	1		ENSP00000448207.1	F8VS61

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1435028

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712424

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 12, 2024

The c.1468C>A (p.Q490K) alteration is located in exon 9 (coding exon 9) of the KRT77 gene. This alteration results from a C to A substitution at nucleotide position 1468, causing the glutamine (Q) at amino acid position 490 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0021

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.052

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.31

M_CAP

Benign

0.0040

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.60

REVEL

Benign

0.042

Sift

Benign

0.098

Sift4G

Benign

0.96

Polyphen

0.61

Vest4

0.22

MutPred

0.32

Loss of sheet (P = 3e-04);

MVP

0.54

MPC

0.24

ClinPred

0.47

GERP RS

3.7

Varity_R

0.18

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over