22-27982536-G-A

Variant names:

• chr22-27982536-G-A
• rs960596602
• NM_001145418.2:c.7131C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001145418.2(TTC28):​c.7131C>T​(p.Ile2377Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,490 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TTC28 NM_001145418.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970
• Publications: 0 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]

TTC28-AS1 (HGNC:29336): (TTC28 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-0.097 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145418.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC28	NM_001145418.2	MANE Select	c.7131C>T	p.Ile2377Ile	synonymous	Exon 23 of 23	NP_001138890.1	Q96AY4
	TTC28	NM_001393403.1		c.7107C>T	p.Ile2369Ile	synonymous	Exon 22 of 22	NP_001380332.1
	TTC28	NM_001393404.1		c.6777C>T	p.Ile2259Ile	synonymous	Exon 22 of 22	NP_001380333.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC28	ENST00000397906.7	TSL:1 MANE Select	c.7131C>T	p.Ile2377Ile	synonymous	Exon 23 of 23	ENSP00000381003.2	Q96AY4
	TTC28-AS1	ENST00000419253.1	TSL:1	n.146-3156G>A		intron	N/A
	TTC28-AS1	ENST00000454741.5	TSL:1	n.206-11937G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399490 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690252

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.0000397 AC: 1 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078992

Other (OTH) AF: 0.00 AC: 0 AN: 58020

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.27
DANN	Benign	0.55
PhyloP100		-0.097

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: rs960596602; hg19: chr22-28378524;