rs768344304

Variant names:

• chr11-1584987-C-A
• rs768344304
• NM_001005922.1:c.263G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-1584987-C-A
• chr11-1584987-C-G
• chr11-1584987-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001005922.1(KRTAP5-1):​c.263G>T​(p.Gly88Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000782 in 1,278,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 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. G88D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 14)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: KRTAP5-1 NM_001005922.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• Publications: 1 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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.263G>T	p.Gly88Val	missense	Exon 1 of 1	NP_001005922.1	Q6L8H4
	KRTAP5-AS1	NR_021489.2		n.328+11919C>A		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.263G>T	p.Gly88Val	missense	Exon 1 of 1	ENSP00000371606.2	Q6L8H4
	KRTAP5-AS1	ENST00000424148.1	TSL:2	n.328+11919C>A		intron	N/A
	KRTAP5-AS1	ENST00000524947.1	TSL:4	n.235-12261C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 14

GnomAD4 exome AF: 7.82e-7 AC: 1 AN: 1278780 Hom.: 0 Cov.: 56 AF XY: 0.00 AC XY: 0 AN XY: 634880

African (AFR) AF: 0.00 AC: 0 AN: 28136

American (AMR) AF: 0.00 AC: 0 AN: 37640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19588

East Asian (EAS) AF: 0.00 AC: 0 AN: 26068

South Asian (SAS) AF: 0.00 AC: 0 AN: 78216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3264

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 994470

Other (OTH) AF: 0.00 AC: 0 AN: 48836

GnomAD4 genome Cov.: 14

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Benign	0.54
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.29	N
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		-0.14
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.070	T
Polyphen		0.98	D
Vest4		0.46
MutPred		0.21		Gain of glycosylation at K86 (P = 0.1526)
MVP		0.22
MPC		0.048
ClinPred		0.33	T
GERP RS		2.8
PromoterAI		0.0052	Neutral
Varity_R		0.13
gMVP		0.048
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.52		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.52		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs768344304; hg19: chr11-1606217;