NM_031962.3:c.236C>G

Variant names:

• chr17-41232737-C-G
• NM_031962.3:c.236C>G

Variant summary

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

The NM_031962.3(KRTAP9-3):​c.236C>G​(p.Pro79Arg) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P79S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP9-3 NM_031962.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.198
• Publications: 0 publications found

Genes affected

KRTAP9-3 (HGNC:16927): (keratin associated protein 9-3) 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=0.12966642).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031962.3. 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
	KRTAP9-3	NM_031962.3	MANE Select	c.236C>G	p.Pro79Arg	missense	Exon 1 of 1	NP_114168.1	Q9BYQ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP9-3	ENST00000411528.4	TSL:6 MANE Select	c.236C>G	p.Pro79Arg	missense	Exon 1 of 1	ENSP00000392189.2	Q9BYQ3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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	0.18
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.0084	N
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.20
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.023
Sift	Benign	0.059	T
Sift4G	Uncertain	0.035	D
Vest4		0.28
MutPred		0.25		Loss of glycosylation at T84 (P = 0.0886)
MVP		0.030
MPC		0.0078
ClinPred		0.16	T
GERP RS		0.73
PromoterAI		-0.0033	Neutral
Varity_R		0.080
gMVP		0.039

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: chr17-39388989;