chr17-41117963-C-G

Variant names:

• chr17-41117963-C-G
• rs533291282
• NM_033059.4:c.353G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033059.4(KRTAP4-11):​c.353G>C​(p.Ser118Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000022 in 1,497,490 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.000041 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000020 (1 hom.)
• Consequence: KRTAP4-11 NM_033059.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.643
• Publications: 1 publications found

Genes affected

KRTAP4-11 (HGNC:18911): (keratin associated protein 4-11) 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, Mar 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015896708).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033059.4. 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
	KRTAP4-11	NM_033059.4	MANE Select	c.353G>C	p.Ser118Thr	missense	Exon 1 of 1	NP_149048.2	Q9BYQ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP4-11	ENST00000391413.4	TSL:6 MANE Select	c.353G>C	p.Ser118Thr	missense	Exon 1 of 1	ENSP00000375232.2	Q9BYQ6

Frequencies

GnomAD3 genomes AF: 0.0000412 AC: 6 AN: 145806 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00120

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000609 AC: 15 AN: 246486 AF XY: 0.0000670

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000715

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000200 AC: 27 AN: 1351586 Hom.: 1 Cov.: 204 AF XY: 0.0000180 AC XY: 12 AN XY: 667190

African (AFR) AF: 0.00 AC: 0 AN: 29154

American (AMR) AF: 0.00 AC: 0 AN: 39174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23476

East Asian (EAS) AF: 0.000613 AC: 22 AN: 35890

South Asian (SAS) AF: 0.0000141 AC: 1 AN: 70686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5022

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1046384

Other (OTH) AF: 0.0000733 AC: 4 AN: 54600

GnomAD4 genome AF: 0.0000411 AC: 6 AN: 145904 Hom.: 0 Cov.: 31 AF XY: 0.0000561 AC XY: 4 AN XY: 71310

African (AFR) AF: 0.00 AC: 0 AN: 36724

American (AMR) AF: 0.00 AC: 0 AN: 14832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00121 AC: 6 AN: 4974

South Asian (SAS) AF: 0.00 AC: 0 AN: 4764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67494

Other (OTH) AF: 0.00 AC: 0 AN: 2024

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.0000517 AC: 6

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	0.11
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Benign	0.53
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.060	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.64
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.041
Sift	Benign	0.24	T
Sift4G	Benign	0.17	T
Polyphen		0.0090	B
Vest4		0.14
MutPred		0.33		Loss of sheet (P = 0.0817)
MVP		0.13
MPC		0.0088
ClinPred		0.021	T
GERP RS		-4.8
PromoterAI		0.0029	Neutral
Varity_R		0.082
gMVP		0.055
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs533291282; hg19: chr17-39274215; COSMIC: COSV66948712;