chr7-120788263-C-T

Variant names:

• chr7-120788263-C-T
• rs1019599323
• NM_012338.4:c.*329G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_012338.4(TSPAN12):​c.*329G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000506 in 355,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: TSPAN12 NM_012338.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.223
• Publications: 0 publications found

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]

TSPAN12 Gene-Disease associations (from GenCC):

• exudative vitreoretinopathy 5

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• TSPAN12-related exudative vitreoretinopathy

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• exudative vitreoretinopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0000591 (9/152204) while in subpopulation NFE AF = 0.000132 (9/68038). AF 95% confidence interval is 0.000068. There are 0 homozygotes in GnomAd4. There are 3 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 9 AD,SD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012338.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN12	NM_012338.4	MANE Select	c.*329G>A		3_prime_UTR	Exon 8 of 8	NP_036470.1	O95859-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN12	ENST00000222747.8	TSL:1 MANE Select	c.*329G>A		3_prime_UTR	Exon 8 of 8	ENSP00000222747.3	O95859-1
	TSPAN12	ENST00000854320.1		c.*329G>A		3_prime_UTR	Exon 9 of 9	ENSP00000524379.1
	TSPAN12	ENST00000854325.1		c.*329G>A		3_prime_UTR	Exon 8 of 8	ENSP00000524384.1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152204 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000443 AC: 9 AN: 203252 Hom.: 0 Cov.: 0 AF XY: 0.0000457 AC XY: 5 AN XY: 109326

African (AFR) AF: 0.00 AC: 0 AN: 5956

American (AMR) AF: 0.000127 AC: 1 AN: 7844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5586

East Asian (EAS) AF: 0.00 AC: 0 AN: 9230

South Asian (SAS) AF: 0.00 AC: 0 AN: 31822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9718

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 814

European-Non Finnish (NFE) AF: 0.0000658 AC: 8 AN: 121600

Other (OTH) AF: 0.00 AC: 0 AN: 10682

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152204 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74356

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15276

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000604

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Exudative vitreoretinopathy 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.57
PhyloP100		-0.22

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: rs1019599323; hg19: chr7-120428317;