22-27982484-A-T

Variant names:

• chr22-27982484-A-T
• rs5762430
• NM_001145418.2:c.7183T>A

Variant summary

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

The NM_001145418.2(TTC28):​c.7183T>A​(p.Leu2395Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TTC28 NM_001145418.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 17 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=0.28576052).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC28	NM_001145418.2	MANE Select	c.7183T>A	p.Leu2395Met	missense	Exon 23 of 23	NP_001138890.1
	TTC28	NM_001393403.1		c.7159T>A	p.Leu2387Met	missense	Exon 22 of 22	NP_001380332.1
	TTC28	NM_001393404.1		c.6829T>A	p.Leu2277Met	missense	Exon 22 of 22	NP_001380333.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC28	ENST00000397906.7	TSL:1 MANE Select	c.7183T>A	p.Leu2395Met	missense	Exon 23 of 23	ENSP00000381003.2
	TTC28-AS1	ENST00000419253.1	TSL:1	n.146-3208A>T		intron	N/A
	TTC28-AS1	ENST00000454741.5	TSL:1	n.206-11989A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	0.58	D
MutationAssessor	Benign	2.0	M
PhyloP100		1.3
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.38	N
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.33
MutPred		0.20		Gain of catalytic residue at V2391 (P = 0.0174)
MVP		0.20
ClinPred		0.87	D
GERP RS		-3.3
Varity_R		0.34
gMVP		0.17
Mutation Taster		=86/14	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: rs5762430; hg19: chr22-28378472;