12-52833923-C-G

Position:

• chr12-52833923-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_175834.3(KRT79):​c.338G>C​(p.Gly113Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: KRT79 NM_175834.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66

Genes affected

KRT79 (HGNC:28930): (keratin 79) 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 skeletal muscle, skin and scalp. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT79	NM_175834.3	c.338G>C	p.Gly113Ala	missense_variant	1/9	ENST00000330553.6	NP_787028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT79	ENST00000330553.6	c.338G>C	p.Gly113Ala	missense_variant	1/9	1	NM_175834.3	ENSP00000328358.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The c.338G>C (p.G113A) alteration is located in exon 1 (coding exon 1) of the KRT79 gene. This alteration results from a G to C substitution at nucleotide position 338, causing the glycine (G) at amino acid position 113 to be replaced by an alanine (A). 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	0.24
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.095	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	0.42	D
MutationAssessor	Pathogenic	4.1	H
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.022	D
Polyphen		0.98	D
Vest4		0.19
MutPred		0.48		Gain of catalytic residue at P110 (P = 0);
MVP		0.74
MPC		0.54
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.76
gMVP		0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs1202939084; hg19: chr12-53227707;