NM_001145418.2:c.102+9524A>C

Variant names:

• chr22-28670098-T-G
• rs9608696
• NM_001145418.2:c.102+9524A>C

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.102+9524A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000022 in 136,534 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000022 (0 hom., cov: 25)
• Consequence: TTC28 NM_001145418.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.483
• 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]

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 (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC28	NM_001145418.2	c.102+9524A>C		intron_variant	Intron 1 of 22	ENST00000397906.7	NP_001138890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC28	ENST00000397906.7	c.102+9524A>C		intron_variant	Intron 1 of 22	1	NM_001145418.2	ENSP00000381003.2
TTC28	ENST00000468807.1	n.191+9524A>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0000220 AC: 3 AN: 136446 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

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: 0.000126

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000319

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000220 AC: 3 AN: 136534 Hom.: 0 Cov.: 25 AF XY: 0.0000304 AC XY: 2 AN XY: 65838

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 37200

American (AMR) AF: 0.00 AC: 0 AN: 13700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3328

East Asian (EAS) AF: 0.00 AC: 0 AN: 4554

South Asian (SAS) AF: 0.00 AC: 0 AN: 4036

European-Finnish (FIN) AF: 0.000126 AC: 1 AN: 7960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.0000319 AC: 2 AN: 62692

Other (OTH) AF: 0.00 AC: 0 AN: 1942

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000843 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.36
PhyloP100		-0.48

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: rs9608696; hg19: chr22-29066086;