22-28538325-T-C

Variant names:

• chr22-28538325-T-C
• rs6005807
• NM_001145418.2:c.381+91227A>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.381+91227A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 152,074 control chromosomes in the GnomAD database, including 60,404 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 0.89 (60404 hom., cov: 30)
• Consequence: TTC28 NM_001145418.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928
• Publications: 14 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]

LOC101929594 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC28	NM_001145418.2	c.381+91227A>G		intron_variant	Intron 2 of 22	ENST00000397906.7	NP_001138890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC28	ENST00000397906.7	c.381+91227A>G		intron_variant	Intron 2 of 22	1	NM_001145418.2	ENSP00000381003.2

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135320 AN: 151956 Hom.: 60356 Cov.: 30

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.926

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.898

Gnomad OTH AF: 0.921

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

GnomAD4 genome AF: 0.891 AC: 135424 AN: 152074 Hom.: 60404 Cov.: 30 AF XY: 0.889 AC XY: 66099 AN XY: 74338

African (AFR) AF: 0.865 AC: 35887 AN: 41484

American (AMR) AF: 0.925 AC: 14147 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.963 AC: 3343 AN: 3472

East Asian (EAS) AF: 0.913 AC: 4702 AN: 5152

South Asian (SAS) AF: 0.887 AC: 4264 AN: 4806

European-Finnish (FIN) AF: 0.843 AC: 8908 AN: 10564

Middle Eastern (MID) AF: 0.962 AC: 281 AN: 292

European-Non Finnish (NFE) AF: 0.898 AC: 61090 AN: 67998

Other (OTH) AF: 0.922 AC: 1944 AN: 2108

Alfa AF: 0.875 Hom.: 7536

Bravo AF: 0.899

Asia WGS AF: 0.902 AC: 3137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.37
PhyloP100		-0.93
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: rs6005807; hg19: chr22-28934313;