rs200620887

Variant names:

• chr17-41034784-C-T
• rs200620887
• NM_030966.2:c.38G>A

Variant summary

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

The NM_030966.2(KRTAP1-3):​c.38G>A​(p.Ser13Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000552 in 1,612,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: KRTAP1-3 NM_030966.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00900
• Publications: 0 publications found

Genes affected

KRTAP1-3 (HGNC:16771): (keratin associated protein 1-3) 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 high sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21. [provided by RefSeq, Jul 2008]

ENSG00000306126 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04947585).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030966.2. 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
	KRTAP1-3	NM_030966.2	MANE Select	c.38G>A	p.Ser13Asn	missense	Exon 1 of 1	NP_112228.1	Q8IUG1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP1-3	ENST00000344363.7	TSL:6 MANE Select	c.38G>A	p.Ser13Asn	missense	Exon 1 of 1	ENSP00000344420.5	Q8IUG1
	ENSG00000306126	ENST00000815517.1		n.220-25515C>T		intron	N/A
	ENSG00000306126	ENST00000815518.1		n.160-25515C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000329 AC: 50 AN: 152068 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000721 AC: 18 AN: 249572 AF XY: 0.0000443

Gnomad AFR exome AF: 0.00110

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1460064 Hom.: 0 Cov.: 35 AF XY: 0.0000220 AC XY: 16 AN XY: 726298

African (AFR) AF: 0.000988 AC: 33 AN: 33398

American (AMR) AF: 0.0000898 AC: 4 AN: 44520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39576

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111108

Other (OTH) AF: 0.00 AC: 0 AN: 60318

GnomAD4 genome AF: 0.000329 AC: 50 AN: 152068 Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24 AN XY: 74278

African (AFR) AF: 0.00118 AC: 49 AN: 41364

American (AMR) AF: 0.00 AC: 0 AN: 15270

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.000309 Hom.: 0

Bravo AF: 0.000434

ESP6500AA AF: 0.000758 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000913 AC: 11

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	-0.62	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	16
DANN	Benign	0.77
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.73	D
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.0090
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.062
Sift	Benign	0.13	T
Sift4G	Uncertain	0.037	D
Vest4		0.24
MVP		0.10
MPC		0.22
ClinPred		0.026	T
GERP RS		-0.18
PromoterAI		0.010	Neutral
gMVP		0.056
Mutation Taster		=97/3	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: rs200620887; hg19: chr17-39191036;