rs2305024

Positions:

• chr18-24082852-A-C
• chr18-24082852-A-G
• chr18-24082852-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TTC39C	NM_001135993.2	c.816-61A>C		intron_variant		ENST00000317571.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC39C	ENST00000317571.8	c.816-61A>C		intron_variant		1	NM_001135993.2	P1
TTC39C	ENST00000304621.10	c.633-61A>C		intron_variant		1
	ENST00000578443.1	n.99-5593T>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR exome AF: 0.552

Gnomad4 AMR exome AF: 0.944

Gnomad4 ASJ exome AF: 0.935

Gnomad4 EAS exome AF: 0.795

Gnomad4 SAS exome AF: 0.784

Gnomad4 FIN exome AF: 0.959

Gnomad4 NFE exome AF: 0.940

Gnomad4 OTH exome AF: 0.895

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

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.907

Gnomad4 ASJ AF: 0.937

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.772

Gnomad4 FIN AF: 0.964

Gnomad4 NFE AF: 0.939

Gnomad4 OTH AF: 0.841

Alfa AF: 0.884 Hom.: 13519

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

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

LitVar

Other links and lift over

dbSNP: rs2305024; hg19: chr18-21662816; COSMIC: COSV58219812; COSMIC: COSV58219812;