17-41487358-T-G

Position:

• chr17-41487358-T-G

Variant summary

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

The NM_003771.5(KRT36):​c.980A>C​(p.His327Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRT36 NM_003771.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.77

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT36	NM_003771.5	c.980A>C	p.His327Pro	missense_variant	5/7	ENST00000328119.11	NP_003762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT36	ENST00000328119.11	c.980A>C	p.His327Pro	missense_variant	5/7	2	NM_003771.5	ENSP00000329165.6
KRT36	ENST00000393986.2	c.830A>C	p.His277Pro	missense_variant	6/8	1		ENSP00000377555.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 19, 2022

The c.980A>C (p.H327P) alteration is located in exon 5 (coding exon 5) of the KRT36 gene. This alteration results from a A to C substitution at nucleotide position 980, causing the histidine (H) at amino acid position 327 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.38	T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Uncertain	0.42	D
MutationAssessor	Pathogenic	3.4	M;.
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-7.4	D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.024	D;D
Sift4G	Benign	0.17	T;T
Polyphen		0.93	P;.
Vest4		0.42
MutPred		0.60		Loss of catalytic residue at M329 (P = 0.0658);.;
MVP		0.74
MPC		0.58
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.92
gMVP		0.82

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: chr17-39643610;