rs201843810

Variant names:

• chr12-52769012-C-A
• rs201843810
• NM_015848.4:c.1618G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-52769012-C-A
• chr12-52769012-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015848.4(KRT76):​c.1618G>T​(p.Gly540Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000677 in 885,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G540S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: KRT76 NM_015848.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44
• Publications: 1 publications found

Genes affected

KRT76 (HGNC:24430): (keratin 76) 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, Jun 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21497145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT76	NM_015848.4	c.1618G>T	p.Gly540Cys	missense_variant	Exon 9 of 9	ENST00000332411.2	NP_056932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT76	ENST00000332411.2	c.1618G>T	p.Gly540Cys	missense_variant	Exon 9 of 9	1	NM_015848.4	ENSP00000330101.2

Frequencies

GnomAD3 genomes AF: 0.00000664 AC: 1 AN: 150644 Hom.: 0 Cov.: 33

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 AF: 0.00000680 AC: 5 AN: 734982 Hom.: 0 Cov.: 10 AF XY: 0.00000259 AC XY: 1 AN XY: 386396

African (AFR) AF: 0.00 AC: 0 AN: 18216

American (AMR) AF: 0.00 AC: 0 AN: 34990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20998

East Asian (EAS) AF: 0.00 AC: 0 AN: 32788

South Asian (SAS) AF: 0.00 AC: 0 AN: 66436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4400

European-Non Finnish (NFE) AF: 0.0000106 AC: 5 AN: 471908

Other (OTH) AF: 0.00 AC: 0 AN: 36078

GnomAD4 genome AF: 0.00000664 AC: 1 AN: 150644 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 73630

African (AFR) AF: 0.00 AC: 0 AN: 40012

American (AMR) AF: 0.00 AC: 0 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2066

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000685 AC: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	0.29
DANN	Benign	0.94
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	0.34	N
PhyloP100		-2.4
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.017	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.20
MutPred		0.46		Gain of catalytic residue at S544 (P = 2e-04);
MVP		0.57
MPC		0.053
ClinPred		0.45	T
GERP RS		-1.6
Varity_R		0.16
gMVP		0.56
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs201843810; hg19: chr12-53162796;