22-28481727-G-T

Position:

• chr22-28481727-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001145418.2(TTC28):​c.381+147825C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,924 control chromosomes in the GnomAD database, including 20,401 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 0.51 (20401 hom., cov: 31)
• Consequence: TTC28 NM_001145418.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC28	NM_001145418.2	c.381+147825C>A		intron_variant		ENST00000397906.7	NP_001138890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC28	ENST00000397906.7	c.381+147825C>A		intron_variant		1	NM_001145418.2	ENSP00000381003	P1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77860 AN: 151806 Hom.: 20386 Cov.: 31

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.513 AC: 77912 AN: 151924 Hom.: 20401 Cov.: 31 AF XY: 0.512 AC XY: 38015 AN XY: 74252

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.473

Alfa AF: 0.479 Hom.: 3256

Bravo AF: 0.491

Asia WGS AF: 0.496 AC: 1730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Benign	0.75

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: rs737622; hg19: chr22-28877715;