NM_198688.3:c.360C>T

Variant names:

• chr21-44592125-G-A
• rs200861871
• NM_198688.3:c.360C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198688.3(KRTAP10-6):​c.360C>T​(p.Cys120Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000298 in 1,342,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: KRTAP10-6 NM_198688.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170

Genes affected

KRTAP10-6 (HGNC:20523): (keratin associated protein 10-6) 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP10-6	NM_198688.3	c.360C>T	p.Cys120Cys	synonymous_variant	Exon 1 of 1	ENST00000400368.1	NP_941961.3
TSPEAR	NM_144991.3	c.83-24120C>T		intron_variant	Intron 1 of 11	ENST00000323084.9	NP_659428.2
TSPEAR	NM_001272037.2	c.-122-24120C>T		intron_variant	Intron 2 of 12		NP_001258966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP10-6	ENST00000400368.1	c.360C>T	p.Cys120Cys	synonymous_variant	Exon 1 of 1	6	NM_198688.3	ENSP00000383219.1
TSPEAR	ENST00000323084.9	c.83-24120C>T		intron_variant	Intron 1 of 11	1	NM_144991.3	ENSP00000321987.4
TSPEAR	ENST00000642437.1	n.*28-24120C>T		intron_variant	Intron 2 of 12			ENSP00000496535.1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD3 exomes AF: 0.00000419 AC: 1 AN: 238944 Hom.: 0 AF XY: 0.00000772 AC XY: 1 AN XY: 129552

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 SAS exome AF: 0.0000337

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000298 AC: 4 AN: 1342622 Hom.: 0 Cov.: 36 AF XY: 0.00000300 AC XY: 2 AN XY: 667692

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000518

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.0
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.35		Position offset: 2

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

Publications

LitVar

Other links and lift over

dbSNP: rs200861871; hg19: chr21-46012006;