17-41255462-C-T

Variant names:

• chr17-41255462-C-T
• NM_030975.2:c.77C>T

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.77C>T​(p.Thr26Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP9-9 NM_030975.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.14
• 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=0.10559088).

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.77C>T	p.Thr26Ile	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.77C>T	p.Thr26Ile	missense	Exon 1 of 1	ENSP00000377576.1	Q9BYP9-3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 147218 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439432 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 715828

African (AFR) AF: 0.00 AC: 0 AN: 32968

American (AMR) AF: 0.00 AC: 0 AN: 43360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25428

East Asian (EAS) AF: 0.00 AC: 0 AN: 38650

South Asian (SAS) AF: 0.00 AC: 0 AN: 84602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4296

European-Non Finnish (NFE) AF: 9.10e-7 AC: 1 AN: 1098778

Other (OTH) AF: 0.00 AC: 0 AN: 58938

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 147218 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 71456

African (AFR) AF: 0.00 AC: 0 AN: 40320

American (AMR) AF: 0.00 AC: 0 AN: 14524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3408

East Asian (EAS) AF: 0.00 AC: 0 AN: 4960

South Asian (SAS) AF: 0.00 AC: 0 AN: 4336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66514

Other (OTH) AF: 0.00 AC: 0 AN: 2004

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	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.88
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.028	N
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.94	T
PhyloP100		-1.1
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.11
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.022	D
Vest4		0.055
MVP		0.12
MPC		0.037
ClinPred		0.091	T
GERP RS		-1.6
PromoterAI		-0.0074	Neutral
gMVP		0.079

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: chr17-39411714;