17-41378102-G-T

Position:

• chr17-41378102-G-T

Variant summary

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

The NM_001386014.1(KRT34):​c.1142C>A​(p.Ser381Tyr) 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. 15/20 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: 0.536

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07846004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT34	NM_001386014.1	c.1142C>A	p.Ser381Tyr	missense_variant	7/7	ENST00000394001.3	NP_001372943.1
KRT34	XM_011524793.3	c.1196C>A	p.Ser399Tyr	missense_variant	8/8		XP_011523095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT34	ENST00000394001.3	c.1142C>A	p.Ser381Tyr	missense_variant	7/7	1	NM_001386014.1	ENSP00000377570.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Apr 09, 2024

The c.1268C>A (p.S423Y) alteration is located in exon 7 (coding exon 7) of the KRT34 gene. This alteration results from a C to A substitution at nucleotide position 1268, causing the serine (S) at amino acid position 423 to be replaced by a tyrosine (Y). 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	0.099
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.87
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.40	T
REVEL	Benign	0.052
Sift4G	Uncertain	0.017	D
Polyphen		0.0010	B
Vest4		0.14
MutPred		0.34		Loss of glycosylation at S423 (P = 0.025);
MVP		0.43
MPC		0.047
ClinPred		0.32	T
GERP RS		0.12
Varity_R		0.079
gMVP		0.29

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: chr17-39534354;