rs750779961

Variant names:

• chr12-52769558-C-G
• rs750779961
• NM_015848.4:c.1510G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-52769558-C-G
• chr12-52769558-C-T

Variant summary

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

The NM_015848.4(KRT76):​c.1510G>C​(p.Val504Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,448 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V504M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: KRT76 NM_015848.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18
• Publications: 0 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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT76	NM_015848.4	c.1510G>C	p.Val504Leu	missense_variant	Exon 8 of 9	ENST00000332411.2	NP_056932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT76	ENST00000332411.2	c.1510G>C	p.Val504Leu	missense_variant	Exon 8 of 9	1	NM_015848.4	ENSP00000330101.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251450 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461448 Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6 AN XY: 727072

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000990 AC: 11 AN: 1111618

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 33

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	0.017	D
MutationAssessor	Benign	0.55	N
PhyloP100		3.2
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.99	D
Vest4		0.62
MutPred		0.37		Gain of catalytic residue at S507 (P = 0.0017);
MVP		0.55
MPC		0.24
ClinPred		0.88	D
GERP RS		3.9
Varity_R		0.31
gMVP		0.53
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs750779961; hg19: chr12-53163342;