chr11-1597800-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004325.2(KRTAP5-2):​c.451G>T​(p.Val151Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V151M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP5-2 NM_001004325.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.900

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0574435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP5-2	NM_001004325.2	c.451G>T	p.Val151Leu	missense_variant	Exon 1 of 1	ENST00000412090.2	NP_001004325.1
KRTAP5-AS1	NR_021489.2	n.881C>A		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP5-2	ENST00000412090.2	c.451G>T	p.Val151Leu	missense_variant	Exon 1 of 1	6	NM_001004325.2	ENSP00000400041.1
KRTAP5-AS1	ENST00000424148.1	n.881C>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
KRTAP5-AS1	ENST00000659213.1	n.646C>A		non_coding_transcript_exon_variant	Exon 2 of 2
KRTAP5-AS1	ENST00000524947.1	n.*217C>A		downstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.9
DANN	Benign	0.65
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.039	N
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.019
Sift4G	Benign	0.21	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.21		Loss of glycosylation at S146 (P = 0.255);
MVP		0.11
MPC		0.086
ClinPred		0.045	T
GERP RS		2.7
Varity_R		0.17
gMVP		0.022

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-1619030;