NM_031961.3:c.204G>C

Variant names:

• chr17-41226858-G-C
• NM_031961.3:c.204G>C

Variant summary

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

The NM_031961.3(KRTAP9-2):​c.204G>C​(p.Gln68His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP9-2 NM_031961.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.35
• Publications: 0 publications found

Genes affected

KRTAP9-2 (HGNC:16926): (keratin associated protein 9-2) 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=0.13064167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP9-2	NM_031961.3	c.204G>C	p.Gln68His	missense_variant	Exon 1 of 1	ENST00000377721.3	NP_114167.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP9-2	ENST00000377721.3	c.204G>C	p.Gln68His	missense_variant	Exon 1 of 1	6	NM_031961.3	ENSP00000366950.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 206

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.204G>C (p.Q68H) alteration is located in exon 1 (coding exon 1) of the KRTAP9-2 gene. This alteration results from a G to C substitution at nucleotide position 204, causing the glutamine (Q) at amino acid position 68 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.4
DANN	Benign	0.92
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.035	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-3.3
PrimateAI	Benign	0.18	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.047
Sift	Uncertain	0.020	D
Sift4G	Benign	0.068	T
Polyphen		0.92	P
Vest4		0.11
MutPred		0.40		Loss of sheet (P = 0.1158);
MVP		0.13
MPC		1.1
ClinPred		0.43	T
GERP RS		-5.6
PromoterAI		0.012	Neutral
Varity_R		0.14
gMVP		0.071

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

hg19: chr17-39383110;