NM_001145418.2:c.7361C>T

Variant names:

• chr22-27982306-G-A
• rs199899926
• NM_001145418.2:c.7361C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145418.2(TTC28):​c.7361C>T​(p.Ala2454Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,523,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: TTC28 NM_001145418.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.26
• Publications: 2 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.049194098).

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.7361C>T	p.Ala2454Val	missense	Exon 23 of 23	NP_001138890.1	Q96AY4
	TTC28	NM_001393403.1		c.7337C>T	p.Ala2446Val	missense	Exon 22 of 22	NP_001380332.1
	TTC28	NM_001393404.1		c.7007C>T	p.Ala2336Val	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.7361C>T	p.Ala2454Val	missense	Exon 23 of 23	ENSP00000381003.2	Q96AY4
	TTC28-AS1	ENST00000419253.1	TSL:1	n.146-3386G>A		intron	N/A
	TTC28-AS1	ENST00000454741.5	TSL:1	n.206-12167G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152136 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000273 AC: 36 AN: 132048 AF XY: 0.000245

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000170

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000521

Gnomad NFE exome AF: 0.000522

Gnomad OTH exome AF: 0.000272

GnomAD4 exome AF: 0.000187 AC: 257 AN: 1371098 Hom.: 0 Cov.: 30 AF XY: 0.000200 AC XY: 135 AN XY: 673800

African (AFR) AF: 0.00 AC: 0 AN: 30602

American (AMR) AF: 0.00 AC: 0 AN: 32034

Ashkenazi Jewish (ASJ) AF: 0.000308 AC: 7 AN: 22748

East Asian (EAS) AF: 0.00 AC: 0 AN: 35504

South Asian (SAS) AF: 0.0000133 AC: 1 AN: 74992

European-Finnish (FIN) AF: 0.000373 AC: 18 AN: 48288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5482

European-Non Finnish (NFE) AF: 0.000211 AC: 225 AN: 1064760

Other (OTH) AF: 0.000106 AC: 6 AN: 56688

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152136 Hom.: 0 Cov.: 31 AF XY: 0.000215 AC XY: 16 AN XY: 74304

African (AFR) AF: 0.0000241 AC: 1 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000432 Hom.: 0

Bravo AF: 0.000151

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000209 AC: 7

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	0.070
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.3
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.22
Sift	Benign	0.042	D
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.029
MVP		0.23
ClinPred		0.040	T
GERP RS		-0.79
Varity_R		0.037
gMVP		0.14
Mutation Taster		=98/2	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: rs199899926; hg19: chr22-28378294; COSMIC: COSV67418142; COSMIC: COSV67418142;