17-40767624-T-C

Variant names:

• chr17-40767624-T-C
• rs1350809013
• NM_181539.5:c.1217A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181539.5(KRT26):​c.1217A>G​(p.Lys406Arg) 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. 15/22 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: 1.95
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09971219).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181539.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT26	NM_181539.5	MANE Select	c.1217A>G	p.Lys406Arg	missense	Exon 7 of 8	NP_853517.2	Q7Z3Y9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT26	ENST00000335552.5	TSL:1 MANE Select	c.1217A>G	p.Lys406Arg	missense	Exon 7 of 8	ENSP00000334798.4	Q7Z3Y9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00080	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.9
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.17
Sift	Benign	0.12	T
Sift4G	Benign	0.41	T
Polyphen		0.017	B
Vest4		0.24
MutPred		0.29		Gain of MoRF binding (P = 0.0662)
MVP		0.13
MPC		0.068
ClinPred		0.21	T
GERP RS		4.9
Varity_R		0.058
gMVP		0.028

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

Other links and lift over

dbSNP: rs1350809013; hg19: chr17-38923876;