22-27982536-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145418.2(TTC28):​c.7131C>G​(p.Ile2377Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,399,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: TTC28 NM_001145418.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06521118).

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>G	p.Ile2377Met	missense	Exon 23 of 23	NP_001138890.1	Q96AY4
	TTC28	NM_001393403.1		c.7107C>G	p.Ile2369Met	missense	Exon 22 of 22	NP_001380332.1
	TTC28	NM_001393404.1		c.6777C>G	p.Ile2259Met	missense	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>G	p.Ile2377Met	missense	Exon 23 of 23	ENSP00000381003.2	Q96AY4
	TTC28-AS1	ENST00000419253.1	TSL:1	n.146-3156G>C		intron	N/A
	TTC28-AS1	ENST00000454741.5	TSL:1	n.206-11937G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000429 AC: 6 AN: 1399490 Hom.: 0 Cov.: 31 AF XY: 0.00000435 AC XY: 3 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: 0.00 AC: 0 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: 0.00000556 AC: 6 AN: 1078992

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	6.8
DANN	Benign	0.70
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.097
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.14
Sift	Benign	0.053	T
Sift4G	Benign	0.20	T
Polyphen		0.26	B
Vest4		0.16
MutPred		0.24		Gain of disorder (P = 0.0172)
MVP		0.20
ClinPred		0.063	T
GERP RS		0.091
Varity_R		0.046
gMVP		0.16
Mutation Taster		=99/1	polymorphism

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;