17-41487086-C-G

Position:

• chr17-41487086-C-G

Variant summary

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

The NM_003771.5(KRT36):​c.1072G>C​(p.Val358Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRT36 NM_003771.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.339

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20923564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT36	NM_003771.5	c.1072G>C	p.Val358Leu	missense_variant	6/7	ENST00000328119.11	NP_003762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT36	ENST00000328119.11	c.1072G>C	p.Val358Leu	missense_variant	6/7	2	NM_003771.5	ENSP00000329165.6
KRT36	ENST00000393986.2	c.922G>C	p.Val308Leu	missense_variant	7/8	1		ENSP00000377555.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Jan 07, 2022

The c.1072G>C (p.V358L) alteration is located in exon 6 (coding exon 6) of the KRT36 gene. This alteration results from a G to C substitution at nucleotide position 1072, causing the valine (V) at amino acid position 358 to be replaced by a leucine (L). 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	Benign	0.34
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.097
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	0.065	N;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.2	N;N
REVEL	Uncertain	0.34
Sift	Benign	0.19	T;T
Sift4G	Benign	0.55	T;T
Polyphen		0.35	B;.
Vest4		0.23
MutPred		0.52		Gain of disorder (P = 0.0912);.;
MVP		0.53
MPC		0.77
ClinPred		0.66	D
GERP RS		6.1
Varity_R		0.15
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-39643338;