rs756171489

Variant names:

• chr11-1584754-C-A
• rs756171489
• NM_001005922.1:c.496G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-1584754-C-A
• chr11-1584754-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001005922.1(KRTAP5-1):​c.496G>T​(p.Ala166Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000573 in 139,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000057 (0 hom., cov: 21)
  • Exomes 𝑓: 0.000057 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP5-1 NM_001005922.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.460
• Publications: 0 publications found

Genes affected

KRTAP5-1 (HGNC:23596): (keratin associated protein 5-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-AS1 (HGNC:27877): (KRTAP5-1/KRTAP5-2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026785314).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005922.1. 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
	KRTAP5-1	NM_001005922.1	MANE Select	c.496G>T	p.Ala166Ser	missense	Exon 1 of 1	NP_001005922.1	Q6L8H4
	KRTAP5-AS1	NR_021489.2		n.328+11686C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-1	ENST00000382171.2	TSL:6 MANE Select	c.496G>T	p.Ala166Ser	missense	Exon 1 of 1	ENSP00000371606.2	Q6L8H4
	KRTAP5-AS1	ENST00000424148.1	TSL:2	n.328+11686C>A		intron	N/A
	KRTAP5-AS1	ENST00000524947.1	TSL:4	n.235-12494C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000573 AC: 8 AN: 139518 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000751

Gnomad ASJ AF: 0.000891

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000614

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000678 AC: 17 AN: 250578 AF XY: 0.0000590

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.000898

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000619

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000573 AC: 83 AN: 1449382 Hom.: 0 Cov.: 93 AF XY: 0.0000541 AC XY: 39 AN XY: 721028

African (AFR) AF: 0.00 AC: 0 AN: 33096

American (AMR) AF: 0.0000227 AC: 1 AN: 44084

Ashkenazi Jewish (ASJ) AF: 0.000856 AC: 22 AN: 25696

East Asian (EAS) AF: 0.00 AC: 0 AN: 39026

South Asian (SAS) AF: 0.00 AC: 0 AN: 85522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52852

Middle Eastern (MID) AF: 0.000229 AC: 1 AN: 4370

European-Non Finnish (NFE) AF: 0.0000507 AC: 56 AN: 1105224

Other (OTH) AF: 0.0000504 AC: 3 AN: 59512

GnomAD4 genome AF: 0.0000573 AC: 8 AN: 139518 Hom.: 0 Cov.: 21 AF XY: 0.0000446 AC XY: 3 AN XY: 67238

African (AFR) AF: 0.00 AC: 0 AN: 36940

American (AMR) AF: 0.0000751 AC: 1 AN: 13318

Ashkenazi Jewish (ASJ) AF: 0.000891 AC: 3 AN: 3366

East Asian (EAS) AF: 0.00 AC: 0 AN: 4550

South Asian (SAS) AF: 0.00 AC: 0 AN: 4218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.0000614 AC: 4 AN: 65192

Other (OTH) AF: 0.00 AC: 0 AN: 1922

Alfa AF: 0.000101 Hom.: 0

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000273

EpiControl AF: 0.000178

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	0.077
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.7
DANN	Benign	0.58
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.095	N
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.90	N
PhyloP100		0.46
PROVEAN	Benign	0.040	N
REVEL	Benign	0.025
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.85	T
Polyphen		0.012	B
Vest4		0.080
MVP		0.20
MPC		0.039
ClinPred		0.076	T
GERP RS		2.5
Varity_R		0.069
gMVP		0.020
Mutation Taster		=96/4	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: rs756171489; hg19: chr11-1605984;