rs9625520

chr22-28641876-C-Achr22-28641876-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.103-12046G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 151,982 control chromosomes in the GnomAD database, including 1,630 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 0.14 (1630 hom., cov: 32)
• Consequence: TTC28 NM_001145418.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.883

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC28	NM_001145418.2	c.103-12046G>T		intron_variant		ENST00000397906.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC28	ENST00000397906.7	c.103-12046G>T		intron_variant		1	NM_001145418.2	P1
TTC28	ENST00000468807.1	n.192-12046G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20543 AN: 151864 Hom.: 1625 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0949

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.0820

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.135 AC: 20563 AN: 151982 Hom.: 1630 Cov.: 32 AF XY: 0.135 AC XY: 10017 AN XY: 74268

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.0954

Gnomad4 ASJ AF: 0.0490

Gnomad4 EAS AF: 0.0100

Gnomad4 SAS AF: 0.0823

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0889 Hom.: 167

Bravo AF: 0.130

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.9
Dann	Benign	0.53

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: rs9625520; hg19: chr22-29037864;