17-41255834-G-C

Variant names:

• chr17-41255834-G-C
• rs1448673304
• NM_030975.2:c.449G>C

Variant summary

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

The NM_030975.2(KRTAP9-9):​c.449G>C​(p.Cys150Ser) 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. 13/20 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. C150F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP9-9 NM_030975.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.537
• Publications: 0 publications found

Genes affected

KRTAP9-9 (HGNC:16773): (keratin associated protein 9-9) 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. Alternative haplotypes of this gene are represented in the GRCh38 reference genome assembly. [provided by RefSeq, Dec 2015]

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=0.104619294).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030975.2. 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
	KRTAP9-9	NM_030975.2	MANE Select	c.449G>C	p.Cys150Ser	missense	Exon 1 of 1	NP_112237.2	Q9BYP9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP9-9	ENST00000394008.1	TSL:6 MANE Select	c.449G>C	p.Cys150Ser	missense	Exon 1 of 1	ENSP00000377576.1	Q9BYP9-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Benign	0.97
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.088	N
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.54
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-7.1	D
REVEL	Benign	0.051
Sift	Benign	0.17	T
Sift4G	Pathogenic	0.0010	D
Vest4		0.24
MVP		0.076
MPC		0.11
ClinPred		0.21	T
GERP RS		-0.49
PromoterAI		0.014	Neutral
gMVP		0.10

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: rs1448673304; hg19: chr17-39412086;