chr17-41065800-C-T

Variant names:

• chr17-41065800-C-T
• rs1188046306
• NM_033184.4:c.46G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_033184.4(KRTAP2-4):​c.46G>A​(p.Gly16Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,529,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000087 (0 hom.)
• Consequence: KRTAP2-4 NM_033184.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.625
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15877652).

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.46G>A	p.Gly16Arg	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.46G>A	p.Gly16Arg	missense	Exon 1 of 1	ENSP00000377583.2	Q9BYR9

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151726 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: 0.000965

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000487 AC: 6 AN: 123154 AF XY: 0.0000456

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000577

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000871 AC: 12 AN: 1378100 Hom.: 0 Cov.: 32 AF XY: 0.00000735 AC XY: 5 AN XY: 679860

African (AFR) AF: 0.00 AC: 0 AN: 31462

American (AMR) AF: 0.00 AC: 0 AN: 35166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24702

East Asian (EAS) AF: 0.000168 AC: 6 AN: 35722

South Asian (SAS) AF: 0.00 AC: 0 AN: 78460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34710

Middle Eastern (MID) AF: 0.000247 AC: 1 AN: 4050

European-Non Finnish (NFE) AF: 0.00000465 AC: 5 AN: 1076310

Other (OTH) AF: 0.00 AC: 0 AN: 57518

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 151726 Hom.: 0 Cov.: 30 AF XY: 0.0000540 AC XY: 4 AN XY: 74094

African (AFR) AF: 0.00 AC: 0 AN: 41338

American (AMR) AF: 0.00 AC: 0 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67848

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

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	0.20
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.27	N
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.63
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.027	D
Vest4		0.36
MutPred		0.70		Loss of loop (P = 0.0986)
MVP		0.34
MPC		0.69
ClinPred		0.18	T
GERP RS		1.8
PromoterAI		-0.0094	Neutral
Varity_R		0.31
gMVP		0.13
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1188046306; hg19: chr17-39222052;