chr21-44600806-A-G

Position:

• chr21-44600806-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198689.3(KRTAP10-7):​c.185A>G​(p.Tyr62Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00853 in 1,570,266 control chromosomes in the GnomAD database, including 2,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.037 (430 hom., cov: 31)
  • Exomes 𝑓: 0.0058 (1670 hom.)
• Consequence: KRTAP10-7 NM_198689.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.165

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=0.003682822).
• BP6: Variant 21-44600806-A-G is Benign according to our data. Variant chr21-44600806-A-G is described in ClinVar as [Benign]. Clinvar id is 1686355.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP10-7	NM_198689.3	c.185A>G	p.Tyr62Cys	missense_variant	1/1	ENST00000609664.2	NP_941962.1
TSPEAR	NM_144991.3	c.83-32801T>C		intron_variant		ENST00000323084.9	NP_659428.2
TSPEAR	NM_001272037.2	c.-122-32801T>C		intron_variant			NP_001258966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP10-7	ENST00000609664.2	c.185A>G	p.Tyr62Cys	missense_variant	1/1	6	NM_198689.3	ENSP00000476821.1
TSPEAR	ENST00000323084.9	c.83-32801T>C		intron_variant		1	NM_144991.3	ENSP00000321987.4
TSPEAR	ENST00000642437.1	n.*28-32801T>C		intron_variant				ENSP00000496535.1

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 4976 AN: 134152 Hom.: 423 Cov.: 31

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.0122

Gnomad EAS AF: 0.00405

Gnomad SAS AF: 0.00883

Gnomad FIN AF: 0.000495

Gnomad MID AF: 0.0135

Gnomad NFE AF: 0.00281

Gnomad OTH AF: 0.0294

GnomAD4 exome AF: 0.00585 AC: 8395 AN: 1436016 Hom.: 1670 Cov.: 32 AF XY: 0.00567 AC XY: 4047 AN XY: 713806

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.00755

Gnomad4 ASJ exome AF: 0.00518

Gnomad4 EAS exome AF: 0.00377

Gnomad4 SAS exome AF: 0.0108

Gnomad4 FIN exome AF: 0.000570

Gnomad4 NFE exome AF: 0.000909

Gnomad4 OTH exome AF: 0.0114

GnomAD4 genome AF: 0.0373 AC: 5006 AN: 134250 Hom.: 430 Cov.: 31 AF XY: 0.0360 AC XY: 2357 AN XY: 65468

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.0172

Gnomad4 ASJ AF: 0.0122

Gnomad4 EAS AF: 0.00406

Gnomad4 SAS AF: 0.00856

Gnomad4 FIN AF: 0.000495

Gnomad4 NFE AF: 0.00281

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.159 Hom.: 149

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

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_noAF	Uncertain	0.010
CADD	Benign	5.2
LIST_S2	Benign	0.031	T
MetaRNN	Benign	0.0037	T
Sift4G	Benign	1.0	T
Vest4		0.11
gMVP		0.043

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4818725; hg19: chr21-46020721;