rs1161588095

Variant names:

• chr17-41065655-C-T
• rs1161588095
• NM_033184.4:c.191G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-41065655-C-T
• chr17-41065655-C-G

Variant summary

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

The NM_033184.4(KRTAP2-4):​c.191G>A​(p.Cys64Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000603 in 1,326,188 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000060 (0 hom.)
• Consequence: KRTAP2-4 NM_033184.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.79
• Publications: 0 publications found

Genes affected

KRTAP2-4 (HGNC:18891): (keratin associated protein 2-4) 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 high 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033184.4. 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
	KRTAP2-4	NM_033184.4	MANE Select	c.191G>A	p.Cys64Tyr	missense	Exon 1 of 1	NP_149440.1	Q9BYR9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP2-4	ENST00000394015.3	TSL:6 MANE Select	c.191G>A	p.Cys64Tyr	missense	Exon 1 of 1	ENSP00000377583.2	Q9BYR9

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.0000102 AC: 1 AN: 97796 AF XY: 0.00

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: 0.0000270

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000603 AC: 8 AN: 1326188 Hom.: 0 Cov.: 29 AF XY: 0.00000462 AC XY: 3 AN XY: 649430

African (AFR) AF: 0.00 AC: 0 AN: 30472

American (AMR) AF: 0.00 AC: 0 AN: 31056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22032

East Asian (EAS) AF: 0.00 AC: 0 AN: 35214

South Asian (SAS) AF: 0.00 AC: 0 AN: 72106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3868

European-Non Finnish (NFE) AF: 0.00000670 AC: 7 AN: 1044068

Other (OTH) AF: 0.0000181 AC: 1 AN: 55322

GnomAD4 genome Cov.: 30

Alfa AF: 0.0000511 Hom.: 0

Bravo AF: 0.0000151

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	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.098	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.76	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.76	T
PhyloP100		2.8
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-9.9	D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.45
MutPred		0.64		Loss of sheet (P = 0.1907)
MVP		0.30
MPC		2.0
ClinPred		1.0	D
GERP RS		4.7
PromoterAI		0.0060	Neutral
Varity_R		0.90
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1161588095; hg19: chr17-39221907; COSMIC: COSV67458617;