rs552890406

Variant names:

• chr17-41047126-G-A
• rs552890406
• NM_001123387.1:c.142C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-41047126-G-A
• chr17-41047126-G-T

Variant summary

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

The NM_001123387.1(KRTAP2-1):​c.142C>T​(p.Pro48Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000727 in 151,346 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 0.000073 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000061 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP2-1 NM_001123387.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.506
• Publications: 1 publications found

Genes affected

KRTAP2-1 (HGNC:16775): (keratin associated protein 2-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000306126 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.009284943).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001123387.1. 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
	KRTAP2-1	NM_001123387.1	MANE Select	c.142C>T	p.Pro48Ser	missense	Exon 1 of 1	NP_001116859.1	Q9BYU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP2-1	ENST00000391419.3	TSL:6 MANE Select	c.142C>T	p.Pro48Ser	missense	Exon 1 of 1	ENSP00000375238.3	Q9BYU5
	ENSG00000306126	ENST00000815517.1		n.220-13173G>A		intron	N/A
	ENSG00000306126	ENST00000815518.1		n.160-13173G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000727 AC: 11 AN: 151228 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000267

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: 0.00

GnomAD2 exomes AF: 0.0000811 AC: 5 AN: 61642 AF XY: 0.0000322

Gnomad AFR exome AF: 0.000891

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0000609 AC: 73 AN: 1199476 Hom.: 0 Cov.: 23 AF XY: 0.0000580 AC XY: 34 AN XY: 586254

African (AFR) AF: 0.000411 AC: 11 AN: 26752

American (AMR) AF: 0.00 AC: 0 AN: 22362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18492

East Asian (EAS) AF: 0.00 AC: 0 AN: 34464

South Asian (SAS) AF: 0.00 AC: 0 AN: 61204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3472

European-Non Finnish (NFE) AF: 0.0000651 AC: 62 AN: 951948

Other (OTH) AF: 0.00 AC: 0 AN: 50618

GnomAD4 genome AF: 0.0000727 AC: 11 AN: 151346 Hom.: 0 Cov.: 31 AF XY: 0.0000676 AC XY: 5 AN XY: 73936

African (AFR) AF: 0.000267 AC: 11 AN: 41246

American (AMR) AF: 0.00 AC: 0 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67730

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.000222 Hom.: 0

ExAC AF: 0.0000951 AC: 1

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	0.081
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.64	D
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.0093	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.24	N
PhyloP100		0.51
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.042
Sift	Benign	0.48	T
Sift4G	Benign	0.73	T
Polyphen		0.19	B
Vest4		0.20
MutPred		0.25		Loss of glycosylation at T45 (P = 0.0494)
MVP		0.12
ClinPred		0.029	T
GERP RS		3.7
PromoterAI		-0.018	Neutral
Varity_R		0.016
gMVP		0.076
Mutation Taster		=94/6	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: rs552890406; hg19: chr17-39203378;