chr18-68715260-G-A

Variant names:

• chr18-68715260-G-A
• rs78924743
• NM_001093729.2:c.-217G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001093729.2(CCDC102B):​c.-217G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00317 in 1,328,876 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (62 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (40 hom.)
• Consequence: CCDC102B NM_001093729.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.986
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 18-68715260-G-A is Benign according to our data. Variant chr18-68715260-G-A is described in ClinVar as [Benign]. Clinvar id is 1260341.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMX3	NM_019022.5	c.-279C>T		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.-279C>T		upstream_gene_variant		1	NM_019022.5	ENSP00000299608.2

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2559 AN: 152196 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00681

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.00141 AC: 1654 AN: 1176562 Hom.: 40 Cov.: 29 AF XY: 0.00130 AC XY: 733 AN XY: 565964

African (AFR) AF: 0.0578 AC: 1364 AN: 23588

American (AMR) AF: 0.00379 AC: 45 AN: 11868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15876

East Asian (EAS) AF: 0.00 AC: 0 AN: 24322

South Asian (SAS) AF: 0.000236 AC: 13 AN: 55116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24186

Middle Eastern (MID) AF: 0.00189 AC: 6 AN: 3168

European-Non Finnish (NFE) AF: 0.0000731 AC: 71 AN: 970662

Other (OTH) AF: 0.00324 AC: 155 AN: 47776

GnomAD4 genome AF: 0.0168 AC: 2562 AN: 152314 Hom.: 62 Cov.: 32 AF XY: 0.0161 AC XY: 1196 AN XY: 74472

African (AFR) AF: 0.0582 AC: 2419 AN: 41570

American (AMR) AF: 0.00680 AC: 104 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68030

Other (OTH) AF: 0.0114 AC: 24 AN: 2112

Alfa AF: 0.00387 Hom.: 1

Bravo AF: 0.0194

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 25, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.86
PhyloP100		0.99
PromoterAI		-0.075	Neutral
Mutation Taster		=299/1	polymorphism

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: rs78924743; hg19: chr18-66382497;