12-52469254-G-C

Variant names:

• chr12-52469254-G-C
• rs410562
• NM_173086.5:c.1503C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173086.5(KRT6C):​c.1503C>G​(p.Ser501Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,032 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: KRT6C NM_173086.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578

Genes affected

KRT6C (HGNC:20406): (keratin 6C) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. The type II keratins are clustered in a region of chromosome 12q13. [provided by RefSeq, Jul 2009]

ACMG classification

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=0.19679657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT6C	NM_173086.5	c.1503C>G	p.Ser501Arg	missense_variant	Exon 9 of 9	ENST00000252250.7	NP_775109.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT6C	ENST00000252250.7	c.1503C>G	p.Ser501Arg	missense_variant	Exon 9 of 9	1	NM_173086.5	ENSP00000252250.6

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152032 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 82

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152032 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74240

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	0.0070
DANN	Benign	0.66
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.069	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	2.0	M
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.50
Sift	Benign	0.31	T
Sift4G	Benign	0.32	T
Polyphen		0.61	P
Vest4		0.34
MutPred		0.45		Gain of catalytic residue at Y497 (P = 0);
MVP		0.46
MPC		0.18
ClinPred		0.68	D
GERP RS		-6.3
Varity_R		0.074
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs410562; hg19: chr12-52863038;