NM_001135993.2:c.461-3915C>G

Variant names:

• chr18-24076670-C-G
• rs8085689
• NM_001135993.2:c.461-3915C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135993.2(TTC39C):​c.461-3915C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 151,828 control chromosomes in the GnomAD database, including 2,694 homozygotes. 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 0.18 (2694 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TTC39C NM_001135993.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250
• Publications: 2 publications found

Genes affected

TTC39C (HGNC:26595): (tetratricopeptide repeat domain 39C) Predicted to be involved in cilium assembly and otolith morphogenesis. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000265204 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC39C	NM_001135993.2	c.461-3915C>G		intron_variant	Intron 4 of 13	ENST00000317571.8	NP_001129465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC39C	ENST00000317571.8	c.461-3915C>G		intron_variant	Intron 4 of 13	1	NM_001135993.2	ENSP00000323645.3
TTC39C	ENST00000304621.10	c.278-3915C>G		intron_variant	Intron 4 of 13	1		ENSP00000306598.6
TTC39C	ENST00000578150.1	n.305-3915C>G		intron_variant	Intron 3 of 3	3
ENSG00000265204	ENST00000578443.1	n.*124G>C		downstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27224 AN: 151708 Hom.: 2692 Cov.: 31

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0163

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.186

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 10 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.179 AC: 27246 AN: 151828 Hom.: 2694 Cov.: 31 AF XY: 0.178 AC XY: 13181 AN XY: 74170

African (AFR) AF: 0.242 AC: 10012 AN: 41338

American (AMR) AF: 0.130 AC: 1979 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 740 AN: 3466

East Asian (EAS) AF: 0.0167 AC: 86 AN: 5150

South Asian (SAS) AF: 0.192 AC: 918 AN: 4780

European-Finnish (FIN) AF: 0.147 AC: 1551 AN: 10552

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11237 AN: 67984

Other (OTH) AF: 0.183 AC: 387 AN: 2114

Alfa AF: 0.0735 Hom.: 83

Bravo AF: 0.179

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.52
PhyloP100		-0.025
Mutation Taster		=100/0	polymorphism (auto)

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: rs8085689; hg19: chr18-21656634;