22-28435931-A-G

Position:

• chr22-28435931-A-G

Variant summary

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

The NM_001145418.2(TTC28):​c.382-129288T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.07 in 152,274 control chromosomes in the GnomAD database, including 549 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 0.070 (549 hom., cov: 32)
• Consequence: TTC28 NM_001145418.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.095 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC28	NM_001145418.2	c.382-129288T>C		intron_variant		ENST00000397906.7	NP_001138890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC28	ENST00000397906.7	c.382-129288T>C		intron_variant		1	NM_001145418.2	ENSP00000381003	P1
TTC28	ENST00000490475.1	n.188+6955T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0700 AC: 10654 AN: 152156 Hom.: 547 Cov.: 32

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0614

Gnomad ASJ AF: 0.0306

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.0917

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0969

Gnomad OTH AF: 0.0507

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

GnomAD4 genome AF: 0.0700 AC: 10663 AN: 152274 Hom.: 549 Cov.: 32 AF XY: 0.0720 AC XY: 5358 AN XY: 74450

Gnomad4 AFR AF: 0.0172

Gnomad4 AMR AF: 0.0619

Gnomad4 ASJ AF: 0.0306

Gnomad4 EAS AF: 0.00443

Gnomad4 SAS AF: 0.0922

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.0969

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0970 Hom.: 220

Bravo AF: 0.0573

Asia WGS AF: 0.0510 AC: 179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.84

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: rs10483151; hg19: chr22-28831919;