rs738996

Positions:

• chr22-28249312-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145418.2(TTC28):​c.933+46886G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,038 control chromosomes in the GnomAD database, including 1,779 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 0.13 (1779 hom., cov: 32)
• Consequence: TTC28 NM_001145418.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134

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=-0.56).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC28	NM_001145418.2	c.933+46886G>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.933+46886G>A		intron_variant		1	NM_001145418.2	ENSP00000381003.2
TTC28	ENST00000612946.4	c.552+46886G>A		intron_variant		5		ENSP00000479834.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19931 AN: 151920 Hom.: 1779 Cov.: 32

Gnomad AFR AF: 0.0355

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.0481

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.131 AC: 19920 AN: 152038 Hom.: 1779 Cov.: 32 AF XY: 0.126 AC XY: 9345 AN XY: 74290

Gnomad4 AFR AF: 0.0354

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.0478

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.141

Alfa AF: 0.140 Hom.: 310

Bravo AF: 0.128

Asia WGS AF: 0.0290 AC: 101 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
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: rs738996; hg19: chr22-28645300;