11-1597800-C-T

Variant names:

• chr11-1597800-C-T
• rs141027563
• NM_001004325.2:c.451G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004325.2(KRTAP5-2):​c.451G>A​(p.Val151Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,424 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V151L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: KRTAP5-2 NM_001004325.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.900
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.075684965).

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.451G>A	p.Val151Met	missense	Exon 1 of 1	NP_001004325.1	Q701N4
	KRTAP5-AS1	NR_021489.2		n.881C>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.451G>A	p.Val151Met	missense	Exon 1 of 1	ENSP00000400041.1	Q701N4
	KRTAP5-AS1	ENST00000424148.1	TSL:2	n.881C>T		non_coding_transcript_exon	Exon 2 of 2
	KRTAP5-AS1	ENST00000659213.1		n.646C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151670 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000398 AC: 10 AN: 251486 AF XY: 0.0000515

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461754 Hom.: 0 Cov.: 29 AF XY: 0.0000138 AC XY: 10 AN XY: 727166

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000378 AC: 15 AN: 39678

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111914

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151670 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74074

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

African (AFR) AF: 0.0000243 AC: 1 AN: 41236

American (AMR) AF: 0.00 AC: 0 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67912

Other (OTH) AF: 0.00 AC: 0 AN: 2084

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00233887), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000225 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000330 AC: 4

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	0.20
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.018	N
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.90
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.035
Sift4G	Uncertain	0.050	T
Polyphen		0.79	P
Vest4		0.18
MVP		0.17
MPC		0.088
ClinPred		0.047	T
GERP RS		2.7
PromoterAI		-0.0070	Neutral
Varity_R		0.068
gMVP		0.023
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: rs141027563; hg19: chr11-1619030; COSMIC: COSV69014835; COSMIC: COSV69014835;