rs5762430

Variant names:

• chr22-27982484-A-G
• rs5762430
• NM_001145418.2:c.7183T>C

Your query was ambiguous. Multiple possible variants found:

• chr22-27982484-A-G
• chr22-27982484-A-T

Variant summary

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

The NM_001145418.2(TTC28):​c.7183T>C​(p.Leu2395Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,551,178 control chromosomes in the GnomAD database, including 30,160 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 0.21 (3774 hom., cov: 31)
  • Exomes 𝑓: 0.18 (26386 hom.)
• Consequence: TTC28 NM_001145418.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

Genes affected

TTC28 (HGNC:29179): (tetratricopeptide repeat domain 28) Enables kinase binding activity. Involved in regulation of mitotic cell cycle. Located in midbody. [provided by Alliance of Genome Resources, Apr 2022]

TTC28-AS1 (HGNC:29336): (TTC28 antisense RNA 1)

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=1.28 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC28	NM_001145418.2	c.7183T>C	p.Leu2395Leu	synonymous_variant	Exon 23 of 23	ENST00000397906.7	NP_001138890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC28	ENST00000397906.7	c.7183T>C	p.Leu2395Leu	synonymous_variant	Exon 23 of 23	1	NM_001145418.2	ENSP00000381003.2

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32112 AN: 151626 Hom.: 3763 Cov.: 31

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.231

GnomAD3 exomes AF: 0.214 AC: 33576 AN: 156602 Hom.: 4156 AF XY: 0.223 AC XY: 18520 AN XY: 82998

Gnomad AFR exome AF: 0.293

Gnomad AMR exome AF: 0.147

Gnomad ASJ exome AF: 0.358

Gnomad EAS exome AF: 0.290

Gnomad SAS exome AF: 0.335

Gnomad FIN exome AF: 0.142

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.234

GnomAD4 exome AF: 0.184 AC: 257578 AN: 1399434 Hom.: 26386 Cov.: 32 AF XY: 0.189 AC XY: 130297 AN XY: 690226

Gnomad4 AFR exome AF: 0.296

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.356

Gnomad4 EAS exome AF: 0.301

Gnomad4 SAS exome AF: 0.335

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.212 AC: 32147 AN: 151744 Hom.: 3774 Cov.: 31 AF XY: 0.212 AC XY: 15745 AN XY: 74144

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.229

Alfa AF: 0.193 Hom.: 5290

Bravo AF: 0.218

Asia WGS AF: 0.338 AC: 1177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.6
DANN	Benign	0.69

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: rs5762430; hg19: chr22-28378472; COSMIC: COSV104431551; COSMIC: COSV104431551;