17-41238442-C-T

Variant names:

• chr17-41238442-C-T
• rs376076348
• NM_031963.3:c.391C>T

Variant summary

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

The NM_031963.3(KRTAP9-8):​c.391C>T​(p.Arg131Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000055 in 1,599,776 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000071 (0 hom., cov: 21)
  • Exomes 𝑓: 0.000060 (0 hom.)
• Consequence: KRTAP9-8 NM_031963.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.71
• Publications: 0 publications found

Genes affected

KRTAP9-8 (HGNC:17231): (keratin associated protein 9-8) 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=0.15549171).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031963.3. 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
	KRTAP9-8	NM_031963.3	MANE Select	c.391C>T	p.Arg131Cys	missense	Exon 1 of 1	NP_114169.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP9-8	ENST00000254072.7	TSL:6 MANE Select	c.391C>T	p.Arg131Cys	missense	Exon 1 of 1	ENSP00000254072.6	Q9BYQ0

Frequencies

GnomAD3 genomes AF: 0.00000713 AC: 1 AN: 140230 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000522 AC: 13 AN: 249276 AF XY: 0.0000518

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000619

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000596 AC: 87 AN: 1459442 Hom.: 0 Cov.: 85 AF XY: 0.0000592 AC XY: 43 AN XY: 726170

African (AFR) AF: 0.00 AC: 0 AN: 31578

American (AMR) AF: 0.0000447 AC: 2 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86206

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53404

Middle Eastern (MID) AF: 0.000350 AC: 2 AN: 5712

European-Non Finnish (NFE) AF: 0.0000603 AC: 67 AN: 1111722

Other (OTH) AF: 0.0000332 AC: 2 AN: 60294

GnomAD4 genome AF: 0.00000713 AC: 1 AN: 140334 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 68256

African (AFR) AF: 0.00 AC: 0 AN: 33178

American (AMR) AF: 0.00 AC: 0 AN: 14442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3424

East Asian (EAS) AF: 0.00 AC: 0 AN: 4878

South Asian (SAS) AF: 0.00 AC: 0 AN: 4520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 66980

Other (OTH) AF: 0.00 AC: 0 AN: 1960

Alfa AF: 0.0000480 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000579 AC: 7

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	-0.46	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.0073	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L
PhyloP100		-2.7
PrimateAI	Benign	0.18	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.061
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.036	D
Polyphen		1.0	D
Vest4		0.12
MVP		0.048
MPC		0.34
ClinPred		0.25	T
GERP RS		-1.4
PromoterAI		0.0037	Neutral
Varity_R		0.12
gMVP		0.062
Mutation Taster		=100/0	polymorphism

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: rs376076348; hg19: chr17-39394694;