rs200384147

Positions:

• chr21-44600667-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_198689.3(KRTAP10-7):​c.46G>A​(p.Gly16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,612,514 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (112 hom.)
• Consequence: KRTAP10-7 NM_198689.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.361

Genes affected

KRTAP10-7 (HGNC:22970): (keratin associated protein 10-7) Enables identical protein binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TSPEAR (HGNC:1268): (thrombospondin type laminin G domain and EAR repeats) This gene encodes a protein that contains a N-terminal thrombospondin-type laminin G domain and several tandem arranged epilepsy-associated repeats (EARs). A mutation in this gene is the cause of autosomal recessive deafness-98. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002353847).
• BP6: Variant 21-44600667-G-A is Benign according to our data. Variant chr21-44600667-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 377277.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00413 (626/151652) while in subpopulation SAS AF= 0.0447 (214/4792). AF 95% confidence interval is 0.0398. There are 11 homozygotes in gnomad4. There are 355 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP10-7	NM_198689.3	c.46G>A	p.Gly16Ser	missense_variant	1/1	ENST00000609664.2	NP_941962.1
TSPEAR	NM_144991.3	c.83-32662C>T		intron_variant		ENST00000323084.9	NP_659428.2
TSPEAR	NM_001272037.2	c.-122-32662C>T		intron_variant			NP_001258966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP10-7	ENST00000609664.2	c.46G>A	p.Gly16Ser	missense_variant	1/1	6	NM_198689.3	ENSP00000476821.1
TSPEAR	ENST00000323084.9	c.83-32662C>T		intron_variant		1	NM_144991.3	ENSP00000321987.4
TSPEAR	ENST00000642437.1	n.*28-32662C>T		intron_variant				ENSP00000496535.1

Frequencies

GnomAD3 genomes AF: 0.00415 AC: 629 AN: 151536 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.00831

Gnomad SAS AF: 0.0450

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00213

Gnomad OTH AF: 0.00529

GnomAD3 exomes AF: 0.00776 AC: 1913 AN: 246598 Hom.: 39 AF XY: 0.00932 AC XY: 1250 AN XY: 134134

Gnomad AFR exome AF: 0.00311

Gnomad AMR exome AF: 0.00108

Gnomad ASJ exome AF: 0.00728

Gnomad EAS exome AF: 0.00736

Gnomad SAS exome AF: 0.0442

Gnomad FIN exome AF: 0.000518

Gnomad NFE exome AF: 0.00207

Gnomad OTH exome AF: 0.00657

GnomAD4 exome AF: 0.00444 AC: 6484 AN: 1460862 Hom.: 112 Cov.: 32 AF XY: 0.00545 AC XY: 3959 AN XY: 726622

Gnomad4 AFR exome AF: 0.00330

Gnomad4 AMR exome AF: 0.00116

Gnomad4 ASJ exome AF: 0.00698

Gnomad4 EAS exome AF: 0.00763

Gnomad4 SAS exome AF: 0.0399

Gnomad4 FIN exome AF: 0.000732

Gnomad4 NFE exome AF: 0.00180

Gnomad4 OTH exome AF: 0.00574

GnomAD4 genome AF: 0.00413 AC: 626 AN: 151652 Hom.: 11 Cov.: 32 AF XY: 0.00479 AC XY: 355 AN XY: 74142

Gnomad4 AFR AF: 0.00385

Gnomad4 AMR AF: 0.00164

Gnomad4 ASJ AF: 0.00721

Gnomad4 EAS AF: 0.00814

Gnomad4 SAS AF: 0.0447

Gnomad4 FIN AF: 0.000566

Gnomad4 NFE AF: 0.00213

Gnomad4 OTH AF: 0.00523

Alfa AF: 0.00311 Hom.: 0

Bravo AF: 0.00326

ESP6500AA AF: 0.00454 AC: 19

ESP6500EA AF: 0.00178 AC: 15

ExAC AF: 0.00862 AC: 1038

EpiCase AF: 0.00240

EpiControl AF: 0.00237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jan 24, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.5
DANN	Benign	0.79
DEOGEN2	Benign	0.068	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.24	T
Sift4G	Benign	0.27	T
Vest4		0.19
MVP		0.24
ClinPred		0.00061	T
GERP RS		-3.3
Varity_R		0.027
gMVP		0.064

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

Publications

LitVar

Other links and lift over

dbSNP: rs200384147; hg19: chr21-46020567; COSMIC: COSV99061373;