22-28228331-T-C

Position:

• chr22-28228331-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC28	NM_001145418.2	c.934-64732A>G		intron_variant		ENST00000397906.7	NP_001138890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC28	ENST00000397906.7	c.934-64732A>G		intron_variant		1	NM_001145418.2	ENSP00000381003.2
TTC28	ENST00000612946.4	c.553-64732A>G		intron_variant		5		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

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.547

Alfa AF: 0.544 Hom.: 35304

Bravo AF: 0.529

Asia WGS AF: 0.578 AC: 2012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.56

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: rs134176; hg19: chr22-28624319;