chr18-68715237-T-C

Variant names:

• chr18-68715237-T-C
• rs309248
• ENST00000582077.5:n.29T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000582077.5(CCDC102B):​n.29T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,338,044 control chromosomes in the GnomAD database, including 21,772 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (9148 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12624 hom.)
• Consequence: CCDC102B ENST00000582077.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.575
• Publications: 4 publications found

Genes affected

CCDC102B (HGNC:26295): (coiled-coil domain containing 102B)

TMX3 (HGNC:24718): (thioredoxin related transmembrane protein 3) This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The canonical protein encoded by this gene has an N-terminal ER-signal sequence, a catalytically active thioredoxin domain, one transmembrane domain and a C-terminal ER-retention sequence. This gene is expressed in many tissues but has its highest expression in heart and skeletal muscle. It is expressed in the retinal neuroepithelium and lens epithelium in the developing murine eye and haploinsufficiency of this gene in humans and zebrafish is associated with microphthalmia. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 18-68715237-T-C is Benign according to our data. Variant chr18-68715237-T-C is described in ClinVar as [Benign]. Clinvar id is 1286457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMX3	NM_019022.5	c.-256A>G		upstream_gene_variant		ENST00000299608.7	NP_061895.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMX3	ENST00000299608.7	c.-256A>G		upstream_gene_variant		1	NM_019022.5	ENSP00000299608.2

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40398 AN: 151884 Hom.: 9120 Cov.: 32

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.0667

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.179

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.121 AC: 143181 AN: 1186042 Hom.: 12624 Cov.: 30 AF XY: 0.118 AC XY: 67625 AN XY: 570992

African (AFR) AF: 0.643 AC: 15135 AN: 23552

American (AMR) AF: 0.214 AC: 2499 AN: 11654

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 3243 AN: 16204

East Asian (EAS) AF: 0.205 AC: 5257 AN: 25680

South Asian (SAS) AF: 0.0614 AC: 3303 AN: 53808

European-Finnish (FIN) AF: 0.121 AC: 3176 AN: 26318

Middle Eastern (MID) AF: 0.154 AC: 494 AN: 3210

European-Non Finnish (NFE) AF: 0.105 AC: 102894 AN: 977110

Other (OTH) AF: 0.148 AC: 7180 AN: 48506

GnomAD4 genome AF: 0.266 AC: 40483 AN: 152002 Hom.: 9148 Cov.: 32 AF XY: 0.263 AC XY: 19514 AN XY: 74320

African (AFR) AF: 0.617 AC: 25572 AN: 41472

American (AMR) AF: 0.213 AC: 3252 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 679 AN: 3468

East Asian (EAS) AF: 0.179 AC: 921 AN: 5132

South Asian (SAS) AF: 0.0661 AC: 318 AN: 4810

European-Finnish (FIN) AF: 0.146 AC: 1546 AN: 10584

Middle Eastern (MID) AF: 0.193 AC: 56 AN: 290

European-Non Finnish (NFE) AF: 0.108 AC: 7366 AN: 67950

Other (OTH) AF: 0.245 AC: 517 AN: 2108

Alfa AF: 0.114 Hom.: 314

Bravo AF: 0.292

Asia WGS AF: 0.189 AC: 658 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.6
DANN	Benign	0.43
PhyloP100		-0.57
PromoterAI		-0.0014	Neutral
Mutation Taster		=300/0	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: rs309248; hg19: chr18-66382474;