NM_001135993.2:c.1187-1692G>A

Variant names:

• chr18-24122142-G-A
• rs2029238
• NM_001135993.2:c.1187-1692G>A

Variant summary

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

The NM_001135993.2(TTC39C):​c.1187-1692G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,004 control chromosomes in the GnomAD database, including 1,288 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 0.12 (1288 hom., cov: 31)
• Consequence: TTC39C NM_001135993.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• Publications: 3 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC39C	NM_001135993.2	c.1187-1692G>A		intron_variant	Intron 8 of 13	ENST00000317571.8	NP_001129465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC39C	ENST00000317571.8	c.1187-1692G>A		intron_variant	Intron 8 of 13	1	NM_001135993.2	ENSP00000323645.3
TTC39C	ENST00000304621.10	c.1004-1692G>A		intron_variant	Intron 8 of 13	1		ENSP00000306598.6
TTC39C	ENST00000540918.3	c.266-1692G>A		intron_variant	Intron 3 of 8	2		ENSP00000443016.1
TTC39C	ENST00000579214.1	c.98-1692G>A		intron_variant	Intron 3 of 3	2		ENSP00000463283.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18456 AN: 151886 Hom.: 1289 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.00367

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.121 AC: 18467 AN: 152004 Hom.: 1288 Cov.: 31 AF XY: 0.122 AC XY: 9074 AN XY: 74274

African (AFR) AF: 0.105 AC: 4362 AN: 41482

American (AMR) AF: 0.101 AC: 1539 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 759 AN: 3466

East Asian (EAS) AF: 0.00368 AC: 19 AN: 5166

South Asian (SAS) AF: 0.224 AC: 1079 AN: 4816

European-Finnish (FIN) AF: 0.115 AC: 1207 AN: 10540

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8874 AN: 67974

Other (OTH) AF: 0.139 AC: 293 AN: 2110

Alfa AF: 0.119 Hom.: 690

Bravo AF: 0.116

Asia WGS AF: 0.0860 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.58
PhyloP100		0.073
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: rs2029238; hg19: chr18-21702106;