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. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145418.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC28	NM_001145418.2	MANE Select	c.7183T>C	p.Leu2395Leu	synonymous	Exon 23 of 23	NP_001138890.1
	TTC28	NM_001393403.1		c.7159T>C	p.Leu2387Leu	synonymous	Exon 22 of 22	NP_001380332.1
	TTC28	NM_001393404.1		c.6829T>C	p.Leu2277Leu	synonymous	Exon 22 of 22	NP_001380333.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC28	ENST00000397906.7	TSL:1 MANE Select	c.7183T>C	p.Leu2395Leu	synonymous	Exon 23 of 23	ENSP00000381003.2
	TTC28-AS1	ENST00000419253.1	TSL:1	n.146-3208A>G		intron	N/A
	TTC28-AS1	ENST00000454741.5	TSL:1	n.206-11989A>G		intron	N/A

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

GnomAD2 exomes AF: 0.214 AC: 33576 AN: 156602 AF XY: 0.223

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 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

African (AFR) AF: 0.296 AC: 9342 AN: 31598

American (AMR) AF: 0.147 AC: 5234 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 8974 AN: 25180

East Asian (EAS) AF: 0.301 AC: 10763 AN: 35738

South Asian (SAS) AF: 0.335 AC: 26550 AN: 79236

European-Finnish (FIN) AF: 0.142 AC: 7019 AN: 49284

Middle Eastern (MID) AF: 0.359 AC: 2047 AN: 5696

European-Non Finnish (NFE) AF: 0.162 AC: 175025 AN: 1078986

Other (OTH) AF: 0.218 AC: 12624 AN: 58012

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

African (AFR) AF: 0.284 AC: 11722 AN: 41342

American (AMR) AF: 0.167 AC: 2552 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1245 AN: 3468

East Asian (EAS) AF: 0.283 AC: 1438 AN: 5090

South Asian (SAS) AF: 0.353 AC: 1688 AN: 4788

European-Finnish (FIN) AF: 0.135 AC: 1427 AN: 10556

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11345 AN: 67902

Other (OTH) AF: 0.229 AC: 483 AN: 2106

Alfa AF: 0.191 Hom.: 10764

Bravo AF: 0.218

Asia WGS AF: 0.338 AC: 1177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.6
DANN	Benign	0.69
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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