NM_031963.3:c.439C>A

Variant names:

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

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>A​(p.Pro147Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000503 in 1,589,934 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000082 (0 hom., cov: 18)
  • Exomes 𝑓: 0.000047 (1 hom.)
• Consequence: KRTAP9-8 NM_031963.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.15021399).

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>A	p.Pro147Thr	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>A	p.Pro147Thr	missense	Exon 1 of 1	ENSP00000254072.6	Q9BYQ0

Frequencies

GnomAD3 genomes AF: 0.0000899 AC: 12 AN: 133490 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000219

Gnomad ASJ AF: 0.000601

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00667

Gnomad NFE AF: 0.0000766

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000764 AC: 18 AN: 235586 AF XY: 0.0000779

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000604

Gnomad ASJ exome AF: 0.000621

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000655

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000474 AC: 69 AN: 1456368 Hom.: 1 Cov.: 46 AF XY: 0.0000649 AC XY: 47 AN XY: 724714

African (AFR) AF: 0.000128 AC: 4 AN: 31276

American (AMR) AF: 0.0000672 AC: 3 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.000575 AC: 15 AN: 26094

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

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53072

Middle Eastern (MID) AF: 0.00165 AC: 9 AN: 5462

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1109912

Other (OTH) AF: 0.000116 AC: 7 AN: 60102

GnomAD4 genome AF: 0.0000824 AC: 11 AN: 133566 Hom.: 0 Cov.: 18 AF XY: 0.0000775 AC XY: 5 AN XY: 64534

African (AFR) AF: 0.00 AC: 0 AN: 30290

American (AMR) AF: 0.000219 AC: 3 AN: 13684

Ashkenazi Jewish (ASJ) AF: 0.000601 AC: 2 AN: 3326

East Asian (EAS) AF: 0.00 AC: 0 AN: 4590

South Asian (SAS) AF: 0.00 AC: 0 AN: 4300

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

Middle Eastern (MID) AF: 0.00360 AC: 1 AN: 278

European-Non Finnish (NFE) AF: 0.0000766 AC: 5 AN: 65244

Other (OTH) AF: 0.00 AC: 0 AN: 1854

Alfa AF: 0.0000960 Hom.: 0

ExAC AF: 0.0000499 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	0.19
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.18
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.044
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.038	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.54		Gain of sheet (P = 0.0477)
MVP		0.030
MPC		0.46
ClinPred		0.64	D
GERP RS		2.3
PromoterAI		0.00060	Neutral
Varity_R		0.26
gMVP		0.084
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;