rs2304589

Positions:

• chr2-19901726-G-A
• chr2-19901726-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001008237.3(TTC32):​c.129C>T​(p.Ser43Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,613,186 control chromosomes in the GnomAD database, including 33,035 homozygotes. 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: 𝑓 0.20 (3402 hom., cov: 33)
  • Exomes 𝑓: 0.19 (29633 hom.)
• Consequence: TTC32 NM_001008237.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13

Genes affected

TTC32 (HGNC:32954): (tetratricopeptide repeat domain 32)

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-2.13 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC32	NM_001008237.3	c.129C>T	p.Ser43Ser	synonymous_variant	1/3	ENST00000333610.4	NP_001008238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC32	ENST00000333610.4	c.129C>T	p.Ser43Ser	synonymous_variant	1/3	1	NM_001008237.3	ENSP00000333018.3
TTC32	ENST00000402414.1	c.129C>T	p.Ser43Ser	synonymous_variant	1/2	5		ENSP00000385708.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30644 AN: 152096 Hom.: 3397 Cov.: 33

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.216

GnomAD3 exomes AF: 0.219 AC: 54574 AN: 249548 Hom.: 7230 AF XY: 0.225 AC XY: 30445 AN XY: 135032

Gnomad AFR exome AF: 0.216

Gnomad AMR exome AF: 0.198

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.418

Gnomad SAS exome AF: 0.387

Gnomad FIN exome AF: 0.164

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.210

GnomAD4 exome AF: 0.188 AC: 274351 AN: 1460972 Hom.: 29633 Cov.: 32 AF XY: 0.194 AC XY: 140753 AN XY: 726676

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.201

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.435

Gnomad4 SAS exome AF: 0.385

Gnomad4 FIN exome AF: 0.161

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.199

GnomAD4 genome AF: 0.202 AC: 30685 AN: 152214 Hom.: 3402 Cov.: 33 AF XY: 0.207 AC XY: 15390 AN XY: 74422

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.217

Alfa AF: 0.159 Hom.: 1731

Bravo AF: 0.202

Asia WGS AF: 0.411 AC: 1426 AN: 3478

EpiCase AF: 0.179

EpiControl AF: 0.179

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.4
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2304589; hg19: chr2-20101487; COSMIC: COSV61267368; COSMIC: COSV61267368;