rs199839459

Variant names:

• chr11-71565891-G-T
• rs199839459
• NM_001012710.2:c.304G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001012710.2(KRTAP5-10):​c.304G>T​(p.Gly102Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.00047 (0 hom., cov: 17)
  • Exomes 𝑓: 0.00095 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP5-10 NM_001012710.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.528
• Publications: 1 publications found

Genes affected

KRTAP5-10 (HGNC:23605): (keratin associated protein 5-10) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.069520354).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012710.2. 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
	KRTAP5-10	NM_001012710.2	MANE Select	c.304G>T	p.Gly102Trp	missense	Exon 1 of 1	NP_001012728.1	Q6L8G5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-10	ENST00000398531.3	TSL:6 MANE Select	c.304G>T	p.Gly102Trp	missense	Exon 1 of 1	ENSP00000381542.1	Q6L8G5

Frequencies

GnomAD3 genomes AF: 0.000468 AC: 56 AN: 119762 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.000226

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000869

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000661

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000780

Gnomad OTH AF: 0.000639

GnomAD2 exomes AF: 0.000570 AC: 138 AN: 242186 AF XY: 0.000555

Gnomad AFR exome AF: 0.000201

Gnomad AMR exome AF: 0.000324

Gnomad ASJ exome AF: 0.000209

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00100

Gnomad OTH exome AF: 0.000170

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000954 AC: 1169 AN: 1225364 Hom.: 4 Cov.: 53 AF XY: 0.000955 AC XY: 580 AN XY: 607070

African (AFR) AF: 0.0000378 AC: 1 AN: 26488

American (AMR) AF: 0.000172 AC: 6 AN: 34870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19678

East Asian (EAS) AF: 0.00 AC: 0 AN: 26208

South Asian (SAS) AF: 0.000507 AC: 39 AN: 76974

European-Finnish (FIN) AF: 0.0000509 AC: 2 AN: 39290

Middle Eastern (MID) AF: 0.000314 AC: 1 AN: 3182

European-Non Finnish (NFE) AF: 0.00114 AC: 1080 AN: 951394

Other (OTH) AF: 0.000846 AC: 40 AN: 47280

GnomAD4 genome AF: 0.000467 AC: 56 AN: 119846 Hom.: 0 Cov.: 17 AF XY: 0.000436 AC XY: 25 AN XY: 57386

African (AFR) AF: 0.000225 AC: 7 AN: 31076

American (AMR) AF: 0.0000868 AC: 1 AN: 11518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3054

East Asian (EAS) AF: 0.00 AC: 0 AN: 3784

South Asian (SAS) AF: 0.000662 AC: 2 AN: 3022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 166

European-Non Finnish (NFE) AF: 0.000780 AC: 45 AN: 57708

Other (OTH) AF: 0.000635 AC: 1 AN: 1576

Alfa AF: 0.000767 Hom.: 0

ESP6500AA AF: 0.000235 AC: 1

ESP6500EA AF: 0.000824 AC: 7

ExAC AF: 0.000374 AC: 45

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	Uncertain	0.42
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.62
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		-0.53
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.27
MVP		0.030
MPC		0.0083
ClinPred		0.090	T
GERP RS		1.9
PromoterAI		-0.015	Neutral
Varity_R		0.040
gMVP		0.027
Mutation Taster		=99/1	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: rs199839459; hg19: chr11-71276937;