rs13058493

Variant names:

• chr22-28098768-T-C
• rs13058493
• NM_001145418.2:c.3547+147A>G

Variant summary

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

The NM_001145418.2(TTC28):​c.3547+147A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0575 in 1,025,890 control chromosomes in the GnomAD database, including 2,234 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 0.077 (659 hom., cov: 32)
  • Exomes 𝑓: 0.054 (1575 hom.)
• Consequence: TTC28 NM_001145418.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC28	NM_001145418.2	c.3547+147A>G		intron_variant	Intron 10 of 22	ENST00000397906.7	NP_001138890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC28	ENST00000397906.7	c.3547+147A>G		intron_variant	Intron 10 of 22	1	NM_001145418.2	ENSP00000381003.2
TTC28	ENST00000612946.4	c.3166+147A>G		intron_variant	Intron 8 of 20	5		ENSP00000479834.1

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11689 AN: 152148 Hom.: 654 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0371

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0567

Gnomad FIN AF: 0.0711

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0542

Gnomad OTH AF: 0.0675

GnomAD4 exome AF: 0.0541 AC: 47274 AN: 873624 Hom.: 1575 AF XY: 0.0541 AC XY: 23692 AN XY: 437838

African (AFR) AF: 0.151 AC: 3046 AN: 20190

American (AMR) AF: 0.0308 AC: 629 AN: 20402

Ashkenazi Jewish (ASJ) AF: 0.0422 AC: 691 AN: 16386

East Asian (EAS) AF: 0.000154 AC: 5 AN: 32388

South Asian (SAS) AF: 0.0577 AC: 3121 AN: 54046

European-Finnish (FIN) AF: 0.0659 AC: 2589 AN: 39286

Middle Eastern (MID) AF: 0.0574 AC: 159 AN: 2772

European-Non Finnish (NFE) AF: 0.0539 AC: 34949 AN: 648658

Other (OTH) AF: 0.0528 AC: 2085 AN: 39496

GnomAD4 genome AF: 0.0769 AC: 11712 AN: 152266 Hom.: 659 Cov.: 32 AF XY: 0.0751 AC XY: 5591 AN XY: 74462

African (AFR) AF: 0.147 AC: 6086 AN: 41532

American (AMR) AF: 0.0371 AC: 567 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 115 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.0569 AC: 275 AN: 4830

European-Finnish (FIN) AF: 0.0711 AC: 755 AN: 10620

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0542 AC: 3689 AN: 68022

Other (OTH) AF: 0.0668 AC: 141 AN: 2112

Alfa AF: 0.0600 Hom.: 389

Bravo AF: 0.0767

Asia WGS AF: 0.0250 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.33
DANN	Benign	0.79
PhyloP100		-0.39
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: rs13058493; hg19: chr22-28494756;