rs746726849

Variant names:

• chr17-41249824-C-T
• rs746726849
• NM_033191.3:c.104C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-41249824-C-T
• chr17-41249824-C-A

Variant summary

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

The NM_033191.3(KRTAP9-4):​c.104C>T​(p.Thr35Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 1,542,966 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: KRTAP9-4 NM_033191.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.187
• Publications: 0 publications found

Genes affected

KRTAP9-4 (HGNC:18902): (keratin associated protein 9-4) 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.053172052).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033191.3. 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
	KRTAP9-4	NM_033191.3	MANE Select	c.104C>T	p.Thr35Ile	missense	Exon 1 of 1	NP_149461.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP9-4	ENST00000334109.3	TSL:6 MANE Select	c.104C>T	p.Thr35Ile	missense	Exon 1 of 1	ENSP00000334922.2	Q9BYQ2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152130 Hom.: 0 Cov.: 32

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: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 250306 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.0000180 AC: 25 AN: 1390836 Hom.: 0 Cov.: 149 AF XY: 0.0000259 AC XY: 18 AN XY: 693790

African (AFR) AF: 0.00 AC: 0 AN: 32036

American (AMR) AF: 0.00 AC: 0 AN: 41026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24876

East Asian (EAS) AF: 0.00 AC: 0 AN: 38062

South Asian (SAS) AF: 0.000177 AC: 15 AN: 84584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53194

Middle Eastern (MID) AF: 0.000623 AC: 3 AN: 4818

European-Non Finnish (NFE) AF: 0.00000474 AC: 5 AN: 1054906

Other (OTH) AF: 0.0000349 AC: 2 AN: 57334

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74320

African (AFR) AF: 0.00 AC: 0 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000153 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000330 AC: 4

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	0.18
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.015	N
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		0.19
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.019
Sift	Benign	0.076	T
Sift4G	Uncertain	0.0060	D
Polyphen		0.026	B
Vest4		0.13
MutPred		0.32		Loss of phosphorylation at T31 (P = 0.0652)
MVP		0.19
MPC		0.095
ClinPred		0.12	T
GERP RS		-1.5
PromoterAI		-0.0042	Neutral
Varity_R		0.099
gMVP		0.081
Mutation Taster		=100/0	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: rs746726849; hg19: chr17-39406076;