chr17-40767601-C-T

Position:

• chr17-40767601-C-T

Variant summary

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

The NM_181539.5(KRT26):​c.1240G>A​(p.Gly414Arg) 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: 33)
• Consequence: KRT26 NM_181539.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.723

Genes affected

KRT26 (HGNC:30840): (keratin 26) The protein encoded by this gene is a member of the keratin superfamily. This keratin protein is a type I keratin that is specific for the inner root sheath of the hair follicle. This gene exists in a cluster with other keratin genes on chromosome 17q21. [provided by RefSeq, Jul 2009]

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=0.15524411).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT26	NM_181539.5	c.1240G>A	p.Gly414Arg	missense_variant	7/8	ENST00000335552.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT26	ENST00000335552.5	c.1240G>A	p.Gly414Arg	missense_variant	7/8	1	NM_181539.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

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 11, 2023

The c.1240G>A (p.G414R) alteration is located in exon 7 (coding exon 7) of the KRT26 gene. This alteration results from a G to A substitution at nucleotide position 1240, causing the glycine (G) at amino acid position 414 to be replaced by an arginine (R). 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	0.078
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0080	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.055
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.16	T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	0.88	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.22
Sift	Benign	0.21	T
Sift4G	Benign	0.18	T
Polyphen		0.92	P
Vest4		0.11
MutPred		0.30		Gain of MoRF binding (P = 0.0338);
MVP		0.52
MPC		0.041
ClinPred		0.74	D
GERP RS		4.9
Varity_R		0.090
gMVP		0.041

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: chr17-38923853;