chr18-24082852-A-C

Variant names:

• chr18-24082852-A-C
• rs2305024
• NM_001135993.2:c.816-61A>C

Variant summary

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

The NM_001135993.2(TTC39C):​c.816-61A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 1,493,744 control chromosomes in the GnomAD database, including 623,490 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 0.82 (53783 hom., cov: 31)
  • Exomes 𝑓: 0.92 (569707 hom.)
• Consequence: TTC39C NM_001135993.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.792
• Publications: 6 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC39C	NM_001135993.2	c.816-61A>C		intron_variant	Intron 5 of 13	ENST00000317571.8	NP_001129465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC39C	ENST00000317571.8	c.816-61A>C		intron_variant	Intron 5 of 13	1	NM_001135993.2	ENSP00000323645.3
TTC39C	ENST00000304621.10	c.633-61A>C		intron_variant	Intron 5 of 13	1		ENSP00000306598.6
ENSG00000265204	ENST00000578443.1	n.99-5593T>G		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125391 AN: 151998 Hom.: 53782 Cov.: 31

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.850

GnomAD4 exome AF: 0.919 AC: 1232292 AN: 1341628 Hom.: 569707 AF XY: 0.916 AC XY: 602091 AN XY: 657320

African (AFR) AF: 0.552 AC: 16577 AN: 30014

American (AMR) AF: 0.944 AC: 30849 AN: 32672

Ashkenazi Jewish (ASJ) AF: 0.935 AC: 19564 AN: 20930

East Asian (EAS) AF: 0.795 AC: 30054 AN: 37796

South Asian (SAS) AF: 0.784 AC: 50851 AN: 64840

European-Finnish (FIN) AF: 0.959 AC: 46763 AN: 48776

Middle Eastern (MID) AF: 0.878 AC: 4620 AN: 5260

European-Non Finnish (NFE) AF: 0.940 AC: 983853 AN: 1046424

Other (OTH) AF: 0.895 AC: 49161 AN: 54916

GnomAD4 genome AF: 0.825 AC: 125421 AN: 152116 Hom.: 53783 Cov.: 31 AF XY: 0.825 AC XY: 61381 AN XY: 74370

African (AFR) AF: 0.569 AC: 23565 AN: 41396

American (AMR) AF: 0.907 AC: 13865 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3251 AN: 3468

East Asian (EAS) AF: 0.781 AC: 4040 AN: 5172

South Asian (SAS) AF: 0.772 AC: 3723 AN: 4822

European-Finnish (FIN) AF: 0.964 AC: 10241 AN: 10618

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.939 AC: 63854 AN: 68028

Other (OTH) AF: 0.841 AC: 1776 AN: 2112

Alfa AF: 0.884 Hom.: 93670

Bravo AF: 0.812

Asia WGS AF: 0.709 AC: 2469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.67
PhyloP100		0.79
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: rs2305024; hg19: chr18-21662816; COSMIC: COSV58219812; COSMIC: COSV58219812;