17-41160495-C-T

Variant names:

• chr17-41160495-C-T
• NM_032524.2:c.197G>A

Variant summary

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

The NM_032524.2(KRTAP4-4):​c.197G>A​(p.Cys66Tyr) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: KRTAP4-4 NM_032524.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.266
• Publications: 0 publications found

Genes affected

KRTAP4-4 (HGNC:16928): (keratin associated protein 4-4) This protein is a member of the keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. KAP family members appear to have unique, family-specific amino- and carboxyl-terminal regions and are subdivided into three multi-gene families according to amino acid composition: the high sulfur, the ultrahigh sulfur, and the high tyrosine/glycine KAPs. This protein is a member of the ultrahigh sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21. [provided by RefSeq, Jul 2008]

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=0.20433128).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032524.2. 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
	KRTAP4-4	NM_032524.2	MANE Select	c.197G>A	p.Cys66Tyr	missense	Exon 1 of 1	NP_115913.1	Q9BYR3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP4-4	ENST00000390661.5	TSL:6 MANE Select	c.197G>A	p.Cys66Tyr	missense	Exon 1 of 1	ENSP00000375076.3	Q9BYR3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

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	0.26
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.58
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	4.6	H
PhyloP100		-0.27
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-9.0	D
REVEL	Benign	0.061
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.65	P
Vest4		0.13
MutPred		0.62		Gain of sheet (P = 0.039)
MVP		0.19
MPC		0.0076
ClinPred		1.0	D
GERP RS		2.5
PromoterAI		0.0068	Neutral
Varity_R		0.82
gMVP		0.080

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

hg19: chr17-39316747;