17-41379076-G-A

Position:

• chr17-41379076-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001386014.1(KRT34):​c.977C>T​(p.Ala326Val) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRT34 NM_001386014.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0720

Genes affected

KRT34 (HGNC:6452): (keratin 34) The protein encoded by this gene is a member of the keratin gene family. As a type I hair keratin, it 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38344926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT34	NM_001386014.1	c.977C>T	p.Ala326Val	missense_variant	6/7	ENST00000394001.3	NP_001372943.1
KRT34	XM_011524793.3	c.1031C>T	p.Ala344Val	missense_variant	7/8		XP_011523095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT34	ENST00000394001.3	c.977C>T	p.Ala326Val	missense_variant	6/7	1	NM_001386014.1	ENSP00000377570.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Dec 14, 2021

The c.1103C>T (p.A368V) alteration is located in exon 6 (coding exon 6) of the KRT34 gene. This alteration results from a C to T substitution at nucleotide position 1103, causing the alanine (A) at amino acid position 368 to be replaced by a valine (V). 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	0.22
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.38	T
REVEL	Benign	0.057
Sift4G	Uncertain	0.054	T
Polyphen		0.99	D
Vest4		0.18
MutPred		0.54		Loss of disorder (P = 0.1246);
MVP		0.61
MPC		0.13
ClinPred		0.55	D
GERP RS		0.37
Varity_R		0.45
gMVP		0.11

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: chr17-39535328;