chr17-41232575-C-T

Variant names:

• chr17-41232575-C-T
• rs371122853
• NM_031962.3:c.74C>T

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.74C>T​(p.Thr25Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,603,602 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T25S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: KRTAP9-3 NM_031962.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.30
• 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=0.086554855).

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.74C>T	p.Thr25Ile	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.74C>T	p.Thr25Ile	missense	Exon 1 of 1	ENSP00000392189.2	Q9BYQ3

Frequencies

GnomAD3 genomes AF: 0.0000270 AC: 4 AN: 148180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000359 AC: 9 AN: 250428 AF XY: 0.0000517

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000117 AC: 17 AN: 1455308 Hom.: 0 Cov.: 37 AF XY: 0.0000138 AC XY: 10 AN XY: 724256

African (AFR) AF: 0.00 AC: 0 AN: 31500

American (AMR) AF: 0.000180 AC: 8 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4882

European-Non Finnish (NFE) AF: 0.00000541 AC: 6 AN: 1109074

Other (OTH) AF: 0.0000499 AC: 3 AN: 60110

GnomAD4 genome AF: 0.0000270 AC: 4 AN: 148294 Hom.: 0 Cov.: 32 AF XY: 0.0000414 AC XY: 3 AN XY: 72524

African (AFR) AF: 0.00 AC: 0 AN: 37798

American (AMR) AF: 0.0000657 AC: 1 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67946

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000414 AC: 5

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	-0.50	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.65
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.024	N
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-1.3
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.046
Sift	Benign	0.087	T
Sift4G	Uncertain	0.039	D
Vest4		0.10
MVP		0.014
MPC		0.0078
ClinPred		0.16	T
GERP RS		-2.2
PromoterAI		0.0047	Neutral
Varity_R		0.10
gMVP		0.053
Mutation Taster		=100/0	polymorphism

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: rs371122853; hg19: chr17-39388827;