rs374671309

Variant names:

• chr11-1585096-C-T
• rs374671309
• NM_001005922.1:c.154G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-1585096-C-T
• chr11-1585096-C-A
• chr11-1585096-C-G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001005922.1(KRTAP5-1):​c.154G>A​(p.Val52Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000771 in 1,542,508 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V52G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 26)
  • Exomes 𝑓: 0.000068 (4 hom.)
• Consequence: KRTAP5-1 NM_001005922.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.157
• Publications: 1 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09637895).
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

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.154G>A	p.Val52Met	missense	Exon 1 of 1	NP_001005922.1	Q6L8H4
	KRTAP5-AS1	NR_021489.2		n.328+12028C>T		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.154G>A	p.Val52Met	missense	Exon 1 of 1	ENSP00000371606.2	Q6L8H4
	KRTAP5-AS1	ENST00000424148.1	TSL:2	n.328+12028C>T		intron	N/A
	KRTAP5-AS1	ENST00000524947.1	TSL:4	n.235-12152C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000175 AC: 22 AN: 126032 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000243

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000247

Gnomad SAS AF: 0.000525

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000132 AC: 32 AN: 241878 AF XY: 0.000145

Gnomad AFR exome AF: 0.000517

Gnomad AMR exome AF: 0.0000930

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000904

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000678 AC: 96 AN: 1416372 Hom.: 4 Cov.: 39 AF XY: 0.0000979 AC XY: 69 AN XY: 704780

African (AFR) AF: 0.000444 AC: 14 AN: 31550

American (AMR) AF: 0.000101 AC: 4 AN: 39680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24466

East Asian (EAS) AF: 0.00 AC: 0 AN: 36130

South Asian (SAS) AF: 0.000771 AC: 64 AN: 83056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52154

Middle Eastern (MID) AF: 0.000411 AC: 2 AN: 4862

European-Non Finnish (NFE) AF: 0.00000460 AC: 5 AN: 1087116

Other (OTH) AF: 0.000122 AC: 7 AN: 57358

GnomAD4 genome AF: 0.000182 AC: 23 AN: 126136 Hom.: 0 Cov.: 26 AF XY: 0.000179 AC XY: 11 AN XY: 61312

African (AFR) AF: 0.000513 AC: 17 AN: 33126

American (AMR) AF: 0.000242 AC: 3 AN: 12376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3088

East Asian (EAS) AF: 0.000248 AC: 1 AN: 4040

South Asian (SAS) AF: 0.000526 AC: 2 AN: 3804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 174

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 59126

Other (OTH) AF: 0.00 AC: 0 AN: 1720

Alfa AF: 0.000921 Hom.: 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	0.24
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Uncertain	0.97
DEOGEN2	Benign	0.021	T
Eigen	Benign	0.019
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.13	N
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.16
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.074
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.22	T
Polyphen		1.0	D
Vest4		0.31
MVP		0.26
MPC		0.042
ClinPred		0.064	T
GERP RS		3.4
PromoterAI		-0.026	Neutral
Varity_R		0.17
gMVP		0.11
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs374671309; hg19: chr11-1606326; COSMIC: COSV66299146;