11-71538586-C-G

Variant names:

• chr11-71538586-C-G
• rs376137869
• NM_021046.3:c.531C>G

Variant summary

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

The NM_021046.3(KRTAP5-8):​c.531C>G​(p.Cys177Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000724 in 1,560,142 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C177F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000063 (1 hom.)
• Consequence: KRTAP5-8 NM_021046.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.789
• Publications: 0 publications found

Genes affected

KRTAP5-8 (HGNC:23603): (keratin associated protein 5-8) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021046.3. 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
	KRTAP5-8	NM_021046.3	MANE Select	c.531C>G	p.Cys177Trp	missense	Exon 1 of 1	NP_066384.2	O75690

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-8	ENST00000398534.4	TSL:6 MANE Select	c.531C>G	p.Cys177Trp	missense	Exon 1 of 1	ENSP00000420723.1	O75690

Frequencies

GnomAD3 genomes AF: 0.000179 AC: 25 AN: 139828 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000661

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000219

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000801 AC: 20 AN: 249648 AF XY: 0.0000741

Gnomad AFR exome AF: 0.000936

Gnomad AMR exome AF: 0.000145

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 AF: 0.0000627 AC: 89 AN: 1420202 Hom.: 1 Cov.: 34 AF XY: 0.0000510 AC XY: 36 AN XY: 705364

African (AFR) AF: 0.00187 AC: 59 AN: 31614

American (AMR) AF: 0.000115 AC: 5 AN: 43474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23524

East Asian (EAS) AF: 0.00 AC: 0 AN: 36854

South Asian (SAS) AF: 0.0000831 AC: 7 AN: 84242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49520

Middle Eastern (MID) AF: 0.000183 AC: 1 AN: 5468

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1087936

Other (OTH) AF: 0.000295 AC: 17 AN: 57570

GnomAD4 genome AF: 0.000172 AC: 24 AN: 139940 Hom.: 0 Cov.: 32 AF XY: 0.000132 AC XY: 9 AN XY: 68278

African (AFR) AF: 0.000659 AC: 24 AN: 36432

American (AMR) AF: 0.00 AC: 0 AN: 14024

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4824

South Asian (SAS) AF: 0.00 AC: 0 AN: 4572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64378

Other (OTH) AF: 0.00 AC: 0 AN: 1930

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000246

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000906 AC: 11

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	0.45
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.9	H
PhyloP100		0.79
PROVEAN	Pathogenic	-9.7	D
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.60	P
Vest4		0.39
MVP		0.081
MPC		0.055
ClinPred		0.76	D
GERP RS		1.8
Varity_R		0.76
gMVP		0.20
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.38		Position offset: -1

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

Other links and lift over

dbSNP: rs376137869; hg19: chr11-71249632;