rs61029972

chr21-44637717-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_181688.3(KRTAP10-10):c.300T>C(p.Cys100=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 848,560 control chromosomes in the GnomAD database, including 1,296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (627 hom., cov: 16)
  • Exomes 𝑓: 0.012 (669 hom.)
• Consequence: KRTAP10-10 NM_181688.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0380

Genes affected

KRTAP10-10 (HGNC:22972): (keratin associated protein 10-10) 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 21-44637717-T-C is Benign according to our data. Variant chr21-44637717-T-C is described in ClinVar as [Benign]. Clinvar id is 403022.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.038 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRTAP10-10	NM_181688.3	c.300T>C	p.Cys100=	synonymous_variant	1/1	ENST00000380095.2
TSPEAR	NM_144991.3	c.83-69712A>G		intron_variant		ENST00000323084.9
TSPEAR	NM_001272037.2	c.-123+52828A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRTAP10-10	ENST00000380095.2	c.300T>C	p.Cys100=	synonymous_variant	1/1		NM_181688.3	P1
TSPEAR	ENST00000323084.9	c.83-69712A>G		intron_variant		1	NM_144991.3	P1
TSPEAR	ENST00000642437.1	c.*27+52828A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.112 AC: 7853 AN: 70116 Hom.: 617 Cov.: 16

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0562

Gnomad ASJ AF: 0.0180

Gnomad EAS AF: 0.00238

Gnomad SAS AF: 0.0190

Gnomad FIN AF: 0.000739

Gnomad MID AF: 0.116

Gnomad NFE AF: 0.00257

Gnomad OTH AF: 0.0946

GnomAD3 exomes AF: 0.0178 AC: 3724 AN: 208662 Hom.: 276 AF XY: 0.0135 AC XY: 1550 AN XY: 114674

Gnomad AFR exome AF: 0.215

Gnomad AMR exome AF: 0.0119

Gnomad ASJ exome AF: 0.00687

Gnomad EAS exome AF: 0.00301

Gnomad SAS exome AF: 0.00776

Gnomad FIN exome AF: 0.000273

Gnomad NFE exome AF: 0.000956

Gnomad OTH exome AF: 0.0133

GnomAD4 exome AF: 0.0118 AC: 9156 AN: 778370 Hom.: 669 Cov.: 93 AF XY: 0.0106 AC XY: 4151 AN XY: 390226

Gnomad4 AFR exome AF: 0.287

Gnomad4 AMR exome AF: 0.0241

Gnomad4 ASJ exome AF: 0.00928

Gnomad4 EAS exome AF: 0.00212

Gnomad4 SAS exome AF: 0.0133

Gnomad4 FIN exome AF: 0.000522

Gnomad4 NFE exome AF: 0.000867

Gnomad4 OTH exome AF: 0.0261

GnomAD4 genome AF: 0.112 AC: 7891 AN: 70190 Hom.: 627 Cov.: 16 AF XY: 0.108 AC XY: 3683 AN XY: 34236

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.0561

Gnomad4 ASJ AF: 0.0180

Gnomad4 EAS AF: 0.00239

Gnomad4 SAS AF: 0.0190

Gnomad4 FIN AF: 0.000739

Gnomad4 NFE AF: 0.00254

Gnomad4 OTH AF: 0.0973

Alfa AF: 0.155 Hom.: 52

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	3.0
Dann	Benign	0.33

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: rs61029972; hg19: chr21-46057634; COSMIC: COSV59951487;