rs134173

Variant names:

• chr22-28222466-A-G
• rs134173
• NM_001145418.2:c.934-58867T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145418.2(TTC28):​c.934-58867T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 152,084 control chromosomes in the GnomAD database, including 20,957 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 0.52 (20957 hom., cov: 33)
• Consequence: TTC28 NM_001145418.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC28	NM_001145418.2	c.934-58867T>C		intron_variant	Intron 5 of 22	ENST00000397906.7	NP_001138890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC28	ENST00000397906.7	c.934-58867T>C		intron_variant	Intron 5 of 22	1	NM_001145418.2	ENSP00000381003.2
TTC28	ENST00000612946.4	c.553-58867T>C		intron_variant	Intron 3 of 20	5		ENSP00000479834.1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79209 AN: 151966 Hom.: 20967 Cov.: 33

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.521 AC: 79222 AN: 152084 Hom.: 20957 Cov.: 33 AF XY: 0.522 AC XY: 38810 AN XY: 74330

African (AFR) AF: 0.430 AC: 17851 AN: 41480

American (AMR) AF: 0.602 AC: 9209 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2092 AN: 3472

East Asian (EAS) AF: 0.554 AC: 2861 AN: 5166

South Asian (SAS) AF: 0.554 AC: 2669 AN: 4814

European-Finnish (FIN) AF: 0.524 AC: 5537 AN: 10564

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37253 AN: 67984

Other (OTH) AF: 0.537 AC: 1135 AN: 2114

Alfa AF: 0.546 Hom.: 20209

Bravo AF: 0.521

Asia WGS AF: 0.566 AC: 1972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.97
DANN	Benign	0.64
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs134173; hg19: chr22-28618454;