rs145691791

Variant names:

• chr11-1584675-C-A
• rs145691791
• NM_001005922.1:c.575G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-1584675-C-A
• chr11-1584675-C-T

Variant summary

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

The NM_001005922.1(KRTAP5-1):​c.575G>T​(p.Gly192Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,107,172 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 0.00053 (0 hom., cov: 21)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: KRTAP5-1 NM_001005922.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012162387).

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.575G>T	p.Gly192Val	missense	Exon 1 of 1	NP_001005922.1	Q6L8H4
	KRTAP5-AS1	NR_021489.2		n.328+11607C>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.575G>T	p.Gly192Val	missense	Exon 1 of 1	ENSP00000371606.2	Q6L8H4
	KRTAP5-AS1	ENST00000424148.1	TSL:2	n.328+11607C>A		intron	N/A
	KRTAP5-AS1	ENST00000524947.1	TSL:4	n.235-12573C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000527 AC: 67 AN: 127068 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00185

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000162

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: 0.0000168

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000213 AC: 52 AN: 243796 AF XY: 0.000182

Gnomad AFR exome AF: 0.00232

Gnomad AMR exome AF: 0.0000615

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000113

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000807

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000112 AC: 110 AN: 979986 Hom.: 0 Cov.: 53 AF XY: 0.0000763 AC XY: 38 AN XY: 498180

African (AFR) AF: 0.00390 AC: 89 AN: 22808

American (AMR) AF: 0.000155 AC: 6 AN: 38826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18570

East Asian (EAS) AF: 0.00 AC: 0 AN: 23006

South Asian (SAS) AF: 0.0000134 AC: 1 AN: 74658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3874

European-Non Finnish (NFE) AF: 0.00000559 AC: 4 AN: 715560

Other (OTH) AF: 0.000252 AC: 10 AN: 39662

GnomAD4 genome AF: 0.000535 AC: 68 AN: 127186 Hom.: 0 Cov.: 21 AF XY: 0.000589 AC XY: 36 AN XY: 61110

African (AFR) AF: 0.00188 AC: 65 AN: 34624

American (AMR) AF: 0.000162 AC: 2 AN: 12338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3108

East Asian (EAS) AF: 0.00 AC: 0 AN: 3454

South Asian (SAS) AF: 0.00 AC: 0 AN: 3262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 242

European-Non Finnish (NFE) AF: 0.0000168 AC: 1 AN: 59630

Other (OTH) AF: 0.00 AC: 0 AN: 1758

Alfa AF: 0.000700 Hom.: 1

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000165 AC: 20

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	0.17
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.71
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.036	N
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.4
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.015
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.10	T
Polyphen		0.22	B
Vest4		0.32
MVP		0.27
MPC		0.048
ClinPred		0.057	T
GERP RS		1.8
Varity_R		0.072
gMVP		0.017
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs145691791; hg19: chr11-1605905;