rs374671309

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005922.1(KRTAP5-1):​c.154G>T​(p.Val52Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,416,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: KRTAP5-1 NM_001005922.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17798147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP5-1	NM_001005922.1	c.154G>T	p.Val52Leu	missense_variant	Exon 1 of 1	ENST00000382171.2	NP_001005922.1
KRTAP5-AS1	NR_021489.2	n.328+12028C>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP5-1	ENST00000382171.2	c.154G>T	p.Val52Leu	missense_variant	Exon 1 of 1	6	NM_001005922.1	ENSP00000371606.2

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD3 exomes AF: 0.0000124 AC: 3 AN: 241878 Hom.: 0 AF XY: 0.0000153 AC XY: 2 AN XY: 131036

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000173

Gnomad SAS 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: 0.00000212 AC: 3 AN: 1416430 Hom.: 0 Cov.: 39 AF XY: 0.00000284 AC XY: 2 AN XY: 704806

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000830

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 26

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	5.5
DANN	Benign	0.94
DEOGEN2	Benign	0.068	T
Eigen	Benign	0.019
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.029	N
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.067
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.41	T
Polyphen		0.98	D
Vest4		0.36
MutPred		0.19		Loss of ubiquitination at K50 (P = 0.1151);
MVP		0.26
MPC		0.041
ClinPred		0.28	T
GERP RS		3.4
Varity_R		0.25
gMVP		0.093

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs374671309; hg19: chr11-1606326;