11-71565898-G-T

Variant names:

• chr11-71565898-G-T
• rs369128313
• NM_001012710.2:c.311G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001012710.2(KRTAP5-10):​c.311G>T​(p.Cys104Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000791 in 1,402,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. C104Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000073 (0 hom., cov: 18)
  • Exomes 𝑓: 0.000087 (0 hom.)
• Consequence: KRTAP5-10 NM_001012710.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.563
• Publications: 0 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02105254).

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.311G>T	p.Cys104Phe	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.311G>T	p.Cys104Phe	missense	Exon 1 of 1	ENSP00000381542.1	Q6L8G5

Frequencies

GnomAD3 genomes AF: 0.00000728 AC: 1 AN: 137350 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000270

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000115 AC: 28 AN: 243656 AF XY: 0.000159

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000869 AC: 110 AN: 1265208 Hom.: 0 Cov.: 55 AF XY: 0.000134 AC XY: 84 AN XY: 626746

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27752

American (AMR) AF: 0.00 AC: 0 AN: 34752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21976

East Asian (EAS) AF: 0.00 AC: 0 AN: 30078

South Asian (SAS) AF: 0.00140 AC: 107 AN: 76346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3538

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 977564

Other (OTH) AF: 0.0000587 AC: 3 AN: 51070

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000728 AC: 1 AN: 137440 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 66638

African (AFR) AF: 0.00 AC: 0 AN: 36508

American (AMR) AF: 0.00 AC: 0 AN: 13892

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3284

East Asian (EAS) AF: 0.00 AC: 0 AN: 4494

South Asian (SAS) AF: 0.000270 AC: 1 AN: 3698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 63114

Other (OTH) AF: 0.00 AC: 0 AN: 1868

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000200 AC: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.82
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		0.56
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.91	P
Vest4		0.24
MutPred		0.28		Gain of glycosylation at S106 (P = 0.0748)
MVP		0.048
MPC		0.0079
ClinPred		0.99	D
GERP RS		1.9
PromoterAI		0.017	Neutral
Varity_R		0.46
gMVP		0.028
Mutation Taster		=97/3	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: rs369128313; hg19: chr11-71276944;