11-1584987-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005922.1(KRTAP5-1):​c.263G>A​(p.Gly88Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,278,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 14)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: KRTAP5-1 NM_001005922.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16228735).

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>A	p.Gly88Asp	missense	Exon 1 of 1	NP_001005922.1	Q6L8H4
	KRTAP5-AS1	NR_021489.2		n.328+11919C>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.263G>A	p.Gly88Asp	missense	Exon 1 of 1	ENSP00000371606.2	Q6L8H4
	KRTAP5-AS1	ENST00000424148.1	TSL:2	n.328+11919C>T		intron	N/A
	KRTAP5-AS1	ENST00000524947.1	TSL:4	n.235-12261C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 14

GnomAD2 exomes AF: 0.0000122 AC: 3 AN: 245870 AF XY: 0.00000751

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: 0.0000272

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000266 AC: 34 AN: 1278780 Hom.: 0 Cov.: 56 AF XY: 0.0000252 AC XY: 16 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: 0.0000322 AC: 32 AN: 994470

Other (OTH) AF: 0.0000410 AC: 2 AN: 48836

GnomAD4 genome Cov.: 14

Alfa AF: 0.0000337 Hom.: 0

ExAC AF: 0.0000165 AC: 2

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	0.19
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.52
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.22	N
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		-0.14
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.054
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.038	D
Polyphen		0.40	B
Vest4		0.48
MutPred		0.24		Gain of ubiquitination at K86 (P = 0.0381)
MVP		0.20
MPC		0.049
ClinPred		0.13	T
GERP RS		2.8
PromoterAI		0.00080	Neutral
Varity_R		0.15
gMVP		0.060
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: rs768344304; hg19: chr11-1606217; COSMIC: COSV101192918;