NM_031963.3:c.439C>T

Variant names:

• chr17-41238490-C-T
• rs778918919
• NM_031963.3:c.439C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_031963.3(KRTAP9-8):​c.439C>T​(p.Pro147Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P147T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 18)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP9-8 NM_031963.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20883515).

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.439C>T	p.Pro147Ser	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.439C>T	p.Pro147Ser	missense	Exon 1 of 1	ENSP00000254072.6	Q9BYQ0

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 133492 Hom.: 0 Cov.: 18

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000424 AC: 1 AN: 235586 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000302

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2 AN: 1456368 Hom.: 0 Cov.: 46 AF XY: 0.00000138 AC XY: 1 AN XY: 724716

African (AFR) AF: 0.00 AC: 0 AN: 31276

American (AMR) AF: 0.0000224 AC: 1 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 86142

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5462

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109914

Other (OTH) AF: 0.00 AC: 0 AN: 60102

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 133492 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 64440

African (AFR) AF: 0.00 AC: 0 AN: 30198

American (AMR) AF: 0.00 AC: 0 AN: 13668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3326

East Asian (EAS) AF: 0.00 AC: 0 AN: 4604

South Asian (SAS) AF: 0.00 AC: 0 AN: 4310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65254

Other (OTH) AF: 0.00 AC: 0 AN: 1832

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.094
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.18
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.065
Sift	Benign	0.040	D
Sift4G	Benign	0.077	T
Polyphen		1.0	D
Vest4		0.16
MutPred		0.55		Gain of glycosylation at P147 (P = 0.0095)
MVP		0.030
MPC		0.72
ClinPred		0.79	D
GERP RS		2.3
PromoterAI		0.0091	Neutral
Varity_R		0.18
gMVP		0.078

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: rs778918919; hg19: chr17-39394742;