chr22-27982652-C-G

Variant names:

• chr22-27982652-C-G
• rs949079098
• NM_001145418.2:c.7015G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001145418.2(TTC28):​c.7015G>C​(p.Ala2339Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2339T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TTC28 NM_001145418.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.75
• Publications: 1 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30988955).

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.7015G>C	p.Ala2339Pro	missense	Exon 23 of 23	NP_001138890.1	Q96AY4
	TTC28	NM_001393403.1		c.6991G>C	p.Ala2331Pro	missense	Exon 22 of 22	NP_001380332.1
	TTC28	NM_001393404.1		c.6661G>C	p.Ala2221Pro	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.7015G>C	p.Ala2339Pro	missense	Exon 23 of 23	ENSP00000381003.2	Q96AY4
	TTC28-AS1	ENST00000419253.1	TSL:1	n.146-3040C>G		intron	N/A
	TTC28-AS1	ENST00000454741.5	TSL:1	n.206-11821C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.087
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	0.31	D
MutationAssessor	Benign	1.8	L
PhyloP100		4.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.013	D
Sift4G	Benign	0.26	T
Polyphen		0.70	P
Vest4		0.29
MutPred		0.16		Gain of catalytic residue at A2339 (P = 0.0185)
MVP		0.34
ClinPred		0.88	D
GERP RS		4.1
Varity_R		0.30
gMVP		0.28
Mutation Taster		=53/47	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: rs949079098; hg19: chr22-28378640;