11-1584751-A-T

Variant names:

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

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>A​(p.Cys167Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C167R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 21)
• Consequence: KRTAP5-1 NM_001005922.1 missense
• Clinical Significance: Not reported in ClinVar
• 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>A	p.Cys167Ser	missense	Exon 1 of 1	NP_001005922.1	Q6L8H4
	KRTAP5-AS1	NR_021489.2		n.328+11683A>T		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>A	p.Cys167Ser	missense	Exon 1 of 1	ENSP00000371606.2	Q6L8H4
	KRTAP5-AS1	ENST00000424148.1	TSL:2	n.328+11683A>T		intron	N/A
	KRTAP5-AS1	ENST00000524947.1	TSL:4	n.235-12497A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 88

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Benign	0.66
DEOGEN2	Benign	0.093	T
Eigen	Benign	0.040
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.19	N
M_CAP	Benign	0.0011	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.094
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.066
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.091	T
Polyphen		1.0	D
Vest4		0.53
MutPred		0.32		Gain of glycosylation at C167 (P = 0.0232)
MVP		0.19
MPC		0.047
ClinPred		0.39	T
GERP RS		3.5
Varity_R		0.60
gMVP		0.041
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs781763244; hg19: chr11-1605981;