NM_031963.3:c.326C>A

Variant names:

• chr17-41238377-C-A
• rs372779791
• NM_031963.3:c.326C>A

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.326C>A​(p.Thr109Lys) 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. 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. T109M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KRTAP9-8 NM_031963.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663
• 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=0.25836214).

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.326C>A	p.Thr109Lys	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.326C>A	p.Thr109Lys	missense	Exon 1 of 1	ENSP00000254072.6	Q9BYQ0

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.077	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.66
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.096
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.37		Gain of solvent accessibility (P = 0.0156)
MVP		0.088
MPC		0.88
ClinPred		0.54	D
GERP RS		1.3
PromoterAI		0.0013	Neutral
Varity_R		0.21
gMVP		0.13

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: rs372779791; hg19: chr17-39394629;