17-41487394-G-C

Variant names:

• chr17-41487394-G-C
• rs2301354
• NM_003771.5:c.944C>G

Variant summary

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

The NM_003771.5(KRT36):​c.944C>G​(p.Thr315Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,868 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KRT36 NM_003771.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646
• Publications: 0 publications found

Genes affected

KRT36 (HGNC:6454): (keratin 36) The protein encoded by this gene is a member of the keratin gene family. This type I hair keratin is an acidic protein which heterodimerizes with type II keratins to form hair and nails. The type I hair keratins are clustered in a region of chromosome 17q12-q21 and have the same direction of transcription. [provided by RefSeq, Jul 2008]

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
KRT36	NM_003771.5	c.944C>G	p.Thr315Arg	missense_variant	Exon 5 of 7	ENST00000328119.11	NP_003762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT36	ENST00000328119.11	c.944C>G	p.Thr315Arg	missense_variant	Exon 5 of 7	2	NM_003771.5	ENSP00000329165.6
KRT36	ENST00000393986.2	c.794C>G	p.Thr265Arg	missense_variant	Exon 6 of 8	1		ENSP00000377555.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460868 Hom.: 0 Cov.: 60 AF XY: 0.00000275 AC XY: 2 AN XY: 726708

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5528

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111650

Other (OTH) AF: 0.00 AC: 0 AN: 60334

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;.
Eigen	Benign	0.052
Eigen_PC	Benign	-0.074
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.36	T;T
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Uncertain	0.75	D
MutationAssessor	Uncertain	2.5	M;.
PhyloP100		-0.65
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-4.9	D;D
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.88	P;.
Vest4		0.34
MutPred		0.48		Gain of MoRF binding (P = 0.053);.;
MVP		0.77
MPC		0.56
ClinPred		0.98	D
GERP RS		1.1
Varity_R		0.90
gMVP		0.53
Mutation Taster		=85/15	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: rs2301354; hg19: chr17-39643646;