7-120788553-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012338.4(TSPAN12):c.*39C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 1,612,734 control chromosomes in the GnomAD database, including 484,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46308 hom., cov: 33)
  • Exomes 𝑓: 0.77 (438036 hom.)
• Consequence: TSPAN12 NM_012338.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.77

Genes affected

TSPAN12 (HGNC:21641): (tetraspanin 12) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 7-120788553-G-A is Benign according to our data. Variant chr7-120788553-G-A is described in ClinVar as [Benign]. Clinvar id is 358760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-120788553-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN12	NM_012338.4	c.*39C>T		3_prime_UTR_variant	8/8	ENST00000222747.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN12	ENST00000222747.8	c.*39C>T		3_prime_UTR_variant	8/8	1	NM_012338.4	P1
TSPAN12	ENST00000415871.5	c.*39C>T		3_prime_UTR_variant	9/9	5		P1
TSPAN12	ENST00000450414.5	c.*807C>T		3_prime_UTR_variant, NMD_transcript_variant	6/6	5

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118284 AN: 152050 Hom.: 46269 Cov.: 33

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.796

GnomAD3 exomes AF: 0.803 AC: 200820 AN: 249984 Hom.: 81453 AF XY: 0.807 AC XY: 109026 AN XY: 135094

Gnomad AFR exome AF: 0.766

Gnomad AMR exome AF: 0.840

Gnomad ASJ exome AF: 0.821

Gnomad EAS exome AF: 0.956

Gnomad SAS exome AF: 0.905

Gnomad FIN exome AF: 0.669

Gnomad NFE exome AF: 0.769

Gnomad OTH exome AF: 0.797

GnomAD4 exome AF: 0.772 AC: 1127830 AN: 1460566 Hom.: 438036 Cov.: 35 AF XY: 0.777 AC XY: 564828 AN XY: 726678

Gnomad4 AFR exome AF: 0.761

Gnomad4 AMR exome AF: 0.840

Gnomad4 ASJ exome AF: 0.816

Gnomad4 EAS exome AF: 0.969

Gnomad4 SAS exome AF: 0.904

Gnomad4 FIN exome AF: 0.678

Gnomad4 NFE exome AF: 0.755

Gnomad4 OTH exome AF: 0.789

GnomAD4 genome AF: 0.778 AC: 118376 AN: 152168 Hom.: 46308 Cov.: 33 AF XY: 0.779 AC XY: 57923 AN XY: 74386

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.845

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.955

Gnomad4 SAS AF: 0.909

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.789

Alfa AF: 0.778 Hom.: 78408

Bravo AF: 0.791

Asia WGS AF: 0.873 AC: 3034 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Exudative vitreoretinopathy 5 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	5.1
Dann	Benign	0.53

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: rs41622; hg19: chr7-120428607;