chr11-1584751-A-G

Variant names:

• chr11-1584751-A-G
• rs781763244
• NM_001005922.1:c.499T>C

Variant summary

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

The NM_001005922.1(KRTAP5-1):​c.499T>C​(p.Cys167Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP5-1 NM_001005922.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0940
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.499T>C	p.Cys167Arg	missense	Exon 1 of 1	NP_001005922.1	Q6L8H4
	KRTAP5-AS1	NR_021489.2		n.328+11683A>G		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.499T>C	p.Cys167Arg	missense	Exon 1 of 1	ENSP00000371606.2	Q6L8H4
	KRTAP5-AS1	ENST00000424148.1	TSL:2	n.328+11683A>G		intron	N/A
	KRTAP5-AS1	ENST00000524947.1	TSL:4	n.235-12497A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.00 AC: 0 AN: 250396 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00000143 AC: 2 AN: 1399650 Hom.: 0 Cov.: 88 AF XY: 0.00000287 AC XY: 2 AN XY: 696010

African (AFR) AF: 0.00 AC: 0 AN: 31692

American (AMR) AF: 0.00 AC: 0 AN: 42530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23856

East Asian (EAS) AF: 0.00 AC: 0 AN: 34370

South Asian (SAS) AF: 0.00 AC: 0 AN: 85036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4102

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1073652

Other (OTH) AF: 0.00 AC: 0 AN: 56180

GnomAD4 genome Cov.: 21

ExAC AF: 0.00000824 AC: 1

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	0.31
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Benign	0.81
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.061	N
M_CAP	Benign	0.0021	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.094
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.74	P
Vest4		0.60
MutPred		0.39		Loss of methylation at K164 (P = 0.0424)
MVP		0.11
MPC		0.062
ClinPred		0.41	T
GERP RS		3.5
Varity_R		0.57
gMVP		0.047
Mutation Taster		=91/9	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: rs781763244; hg19: chr11-1605981;