rs41278845

Variant names:

• chr22-27982396-G-A
• rs41278845
• NM_001145418.2:c.7271C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-27982396-G-A
• chr22-27982396-G-C
• chr22-27982396-G-T

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.7271C>T​(p.Ala2424Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,240 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. 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. A2424G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TTC28 NM_001145418.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304

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=0.037222028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC28	NM_001145418.2	c.7271C>T	p.Ala2424Val	missense_variant	Exon 23 of 23	ENST00000397906.7	NP_001138890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC28	ENST00000397906.7	c.7271C>T	p.Ala2424Val	missense_variant	Exon 23 of 23	1	NM_001145418.2	ENSP00000381003.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399240 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 690136

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: 25174

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: 49124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078968

Other (OTH) AF: 0.00 AC: 0 AN: 58000

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.26
DANN	Benign	0.76
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.037	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.55	.;N
PhyloP100		0.30
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.28	.;N
REVEL	Benign	0.18
Sift	Benign	0.42	.;T
Sift4G	Benign	0.67	T;T
Polyphen		0.0	.;B
Vest4		0.031
MutPred		0.090		.;Loss of glycosylation at P2425 (P = 0.0963);
MVP		0.17
ClinPred		0.019	T
GERP RS		0.18
Varity_R		0.023
gMVP		0.085
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

Publications

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Other links and lift over

dbSNP: rs41278845; hg19: chr22-28378384;