22-27982844-C-G

Variant names:

• chr22-27982844-C-G
• rs1431610934
• NM_001145418.2:c.6823G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001145418.2(TTC28):​c.6823G>C​(p.Asp2275His) variant causes a missense change. The variant allele was found at a frequency of 0.00000144 in 1,389,128 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D2275N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TTC28 NM_001145418.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.68
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.6823G>C	p.Asp2275His	missense	Exon 23 of 23	NP_001138890.1	Q96AY4
	TTC28	NM_001393403.1		c.6799G>C	p.Asp2267His	missense	Exon 22 of 22	NP_001380332.1
	TTC28	NM_001393404.1		c.6469G>C	p.Asp2157His	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.6823G>C	p.Asp2275His	missense	Exon 23 of 23	ENSP00000381003.2	Q96AY4
	TTC28-AS1	ENST00000419253.1	TSL:1	n.146-2848C>G		intron	N/A
	TTC28-AS1	ENST00000454741.5	TSL:1	n.206-11629C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1389128 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 683882

African (AFR) AF: 0.00 AC: 0 AN: 31364

American (AMR) AF: 0.00 AC: 0 AN: 35096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24268

East Asian (EAS) AF: 0.00 AC: 0 AN: 35628

South Asian (SAS) AF: 0.00 AC: 0 AN: 77820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1072932

Other (OTH) AF: 0.00 AC: 0 AN: 57490

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	0.53	D
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.7
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.071	T
Polyphen		0.81	P
Vest4		0.35
MutPred		0.13		Gain of glycosylation at P2272 (P = 0.1213)
MVP		0.45
ClinPred		0.86	D
GERP RS		5.0
Varity_R		0.13
gMVP		0.23
Mutation Taster		=68/32	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: rs1431610934; hg19: chr22-28378832;