17-41255476-C-T

Variant names:

• chr17-41255476-C-T
• rs530523565
• NM_030975.2:c.91C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_030975.2(KRTAP9-9):​c.91C>T​(p.Pro31Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000308 in 1,592,012 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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. P31T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (1 hom., cov: 30)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: KRTAP9-9 NM_030975.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014632046).

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.91C>T	p.Pro31Ser	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.91C>T	p.Pro31Ser	missense	Exon 1 of 1	ENSP00000377576.1	Q9BYP9-3

Frequencies

GnomAD3 genomes AF: 0.0000201 AC: 3 AN: 148922 Hom.: 1 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: 0.000400

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000438 AC: 11 AN: 250870 AF XY: 0.0000590

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000436

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000319 AC: 46 AN: 1442962 Hom.: 0 Cov.: 36 AF XY: 0.0000307 AC XY: 22 AN XY: 717740

African (AFR) AF: 0.0000606 AC: 2 AN: 33008

American (AMR) AF: 0.0000689 AC: 3 AN: 43564

Ashkenazi Jewish (ASJ) AF: 0.0000392 AC: 1 AN: 25490

East Asian (EAS) AF: 0.000387 AC: 15 AN: 38734

South Asian (SAS) AF: 0.00 AC: 0 AN: 85090

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4494

European-Non Finnish (NFE) AF: 0.0000182 AC: 20 AN: 1100776

Other (OTH) AF: 0.0000677 AC: 4 AN: 59114

GnomAD4 genome AF: 0.0000201 AC: 3 AN: 149050 Hom.: 1 Cov.: 30 AF XY: 0.0000276 AC XY: 2 AN XY: 72546

African (AFR) AF: 0.00 AC: 0 AN: 40794

American (AMR) AF: 0.00 AC: 0 AN: 14852

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3430

East Asian (EAS) AF: 0.000401 AC: 2 AN: 4990

South Asian (SAS) AF: 0.00 AC: 0 AN: 4552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67080

Other (OTH) AF: 0.00 AC: 0 AN: 2056

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000494 AC: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.4
DANN	Benign	0.92
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0021	N
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.95	T
PhyloP100		-1.3
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.040
Sift	Benign	0.80	T
Sift4G	Benign	1.0	T
Vest4		0.044
MVP		0.12
MPC		0.035
ClinPred		0.014	T
GERP RS		-2.6
PromoterAI		0.0066	Neutral
gMVP		0.044
Mutation Taster		=99/1	polymorphism

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: rs530523565; hg19: chr17-39411728;