12-52691428-T-G

Variant names:

• chr12-52691428-T-G
• NM_175078.3:c.1474A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_175078.3(KRT77):​c.1474A>C​(p.Ser492Arg) 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. 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 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36497784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT77	NM_175078.3	c.1474A>C	p.Ser492Arg	missense_variant	Exon 9 of 9	ENST00000341809.8	NP_778253.2
KRT77	XM_011538288.3	c.775A>C	p.Ser259Arg	missense_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.1474A>C	p.Ser492Arg	missense_variant	Exon 9 of 9	1	NM_175078.3	ENSP00000342710.3
KRT77	ENST00000553168.1	n.*812A>C		non_coding_transcript_exon_variant	Exon 10 of 10	1		ENSP00000448207.1
KRT77	ENST00000553168.1	n.*812A>C		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
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.36	T
MetaSVM	Uncertain	0.031	D
MutationAssessor	Uncertain	2.8	M
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.058	T
Polyphen		1.0	D
Vest4		0.41
MutPred		0.31		Loss of sheet (P = 3e-04);
MVP		0.90
MPC		0.21
ClinPred		0.92	D
GERP RS		3.7
Varity_R		0.26
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-53085212;