rs1258475561

Variant names:

• chr11-1597982-G-T
• rs1258475561
• NM_001004325.2:c.269C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-1597982-G-T
• chr11-1597982-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004325.2(KRTAP5-2):​c.269C>A​(p.Ser90Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000533 in 1,312,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000074 (0 hom., cov: 22)
  • Exomes 𝑓: 0.0000053 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP5-2 NM_001004325.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.493
• Publications: 0 publications found

Genes affected

KRTAP5-2 (HGNC:23597): (keratin associated protein 5-2) 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2004605).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004325.2. 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
	KRTAP5-2	NM_001004325.2	MANE Select	c.269C>A	p.Ser90Tyr	missense	Exon 1 of 1	NP_001004325.1	Q701N4
	KRTAP5-AS1	NR_021489.2		n.1063G>T		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-2	ENST00000412090.2	TSL:6 MANE Select	c.269C>A	p.Ser90Tyr	missense	Exon 1 of 1	ENSP00000400041.1	Q701N4
	KRTAP5-AS1	ENST00000424148.1	TSL:2	n.1063G>T		non_coding_transcript_exon	Exon 2 of 2
	KRTAP5-AS1	ENST00000792906.1		n.214-14383G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000739 AC: 1 AN: 135352 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000282

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: 0.00000401 AC: 1 AN: 249554 AF XY: 0.00

Gnomad AFR exome AF: 0.0000649

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 AF: 0.00000533 AC: 7 AN: 1312874 Hom.: 0 Cov.: 54 AF XY: 0.00000459 AC XY: 3 AN XY: 652938

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000165 AC: 5 AN: 30330

American (AMR) AF: 0.0000240 AC: 1 AN: 41630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24334

East Asian (EAS) AF: 0.00 AC: 0 AN: 36294

South Asian (SAS) AF: 0.00 AC: 0 AN: 78044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4434

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 995212

Other (OTH) AF: 0.0000184 AC: 1 AN: 54276

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000227035), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000739 AC: 1 AN: 135352 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 65556

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000282 AC: 1 AN: 35452

American (AMR) AF: 0.00 AC: 0 AN: 13188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3314

East Asian (EAS) AF: 0.00 AC: 0 AN: 4586

South Asian (SAS) AF: 0.00 AC: 0 AN: 3982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 244

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62940

Other (OTH) AF: 0.00 AC: 0 AN: 1842

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

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	-0.33	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.85
DEOGEN2	Benign	0.096	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.12	N
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		-0.49
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.082
Sift4G	Uncertain	0.0030	D
Polyphen		0.98	D
Vest4		0.35
MutPred		0.27		Loss of phosphorylation at S90 (P = 0.0165)
MVP		0.16
MPC		0.11
ClinPred		0.22	T
GERP RS		2.8
Varity_R		0.21
gMVP		0.041
Mutation Taster		=98/2	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: rs1258475561; hg19: chr11-1619212;