NM_001145418.2:c.934-64732A>G

Variant names:

• chr22-28228331-T-C
• rs134176
• NM_001145418.2:c.934-64732A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145418.2(TTC28):​c.934-64732A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,002 control chromosomes in the GnomAD database, including 21,411 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 0.53 (21411 hom., cov: 32)
• Consequence: TTC28 NM_001145418.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.597 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.934-64732A>G		intron	N/A	NP_001138890.1
	TTC28	NM_001393403.1		c.934-64732A>G		intron	N/A	NP_001380332.1
	TTC28	NM_001393404.1		c.580-64732A>G		intron	N/A	NP_001380333.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC28	ENST00000397906.7	TSL:1 MANE Select	c.934-64732A>G		intron	N/A	ENSP00000381003.2
	TTC28	ENST00000612946.4	TSL:5	c.553-64732A>G		intron	N/A	ENSP00000479834.1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80189 AN: 151884 Hom.: 21412 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.546

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.528 AC: 80219 AN: 152002 Hom.: 21411 Cov.: 32 AF XY: 0.530 AC XY: 39395 AN XY: 74286

African (AFR) AF: 0.468 AC: 19405 AN: 41448

American (AMR) AF: 0.607 AC: 9267 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2056 AN: 3470

East Asian (EAS) AF: 0.549 AC: 2842 AN: 5176

South Asian (SAS) AF: 0.574 AC: 2760 AN: 4806

European-Finnish (FIN) AF: 0.533 AC: 5627 AN: 10560

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36483 AN: 67960

Other (OTH) AF: 0.547 AC: 1155 AN: 2112

Alfa AF: 0.542 Hom.: 46092

Bravo AF: 0.529

Asia WGS AF: 0.578 AC: 2012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.56
PhyloP100		-0.29
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: rs134176; hg19: chr22-28624319;