rs41623

Variant names:

• chr7-120788745-C-A
• rs41623
• NM_012338.4:c.765G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-120788745-C-A
• chr7-120788745-C-T
• chr7-120788745-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_012338.4(TSPAN12):​c.765G>T​(p.Pro255Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 1,613,870 control chromosomes in the GnomAD database, including 478,048 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P255P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.78 (46556 hom., cov: 31)
  • Exomes 𝑓: 0.77 (431492 hom.)
• Consequence: TSPAN12 NM_012338.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.215
• Publications: 28 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 7-120788745-C-A is Benign according to our data. Variant chr7-120788745-C-A is described in ClinVar as Benign. ClinVar VariationId is 260253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.215 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

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.765G>T	p.Pro255Pro	synonymous	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.765G>T	p.Pro255Pro	synonymous	Exon 8 of 8	ENSP00000222747.3	O95859-1
	TSPAN12	ENST00000415871.5	TSL:5	c.765G>T	p.Pro255Pro	synonymous	Exon 9 of 9	ENSP00000397699.1	O95859-1
	TSPAN12	ENST00000854320.1		c.765G>T	p.Pro255Pro	synonymous	Exon 9 of 9	ENSP00000524379.1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118513 AN: 151936 Hom.: 46516 Cov.: 31

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.799

GnomAD2 exomes AF: 0.801 AC: 201370 AN: 251340 AF XY: 0.805

Gnomad AFR exome AF: 0.789

Gnomad AMR exome AF: 0.839

Gnomad ASJ exome AF: 0.821

Gnomad EAS exome AF: 0.957

Gnomad FIN exome AF: 0.665

Gnomad NFE exome AF: 0.763

Gnomad OTH exome AF: 0.794

GnomAD4 exome AF: 0.766 AC: 1119499 AN: 1461816 Hom.: 431492 Cov.: 77 AF XY: 0.771 AC XY: 560812 AN XY: 727212

African (AFR) AF: 0.784 AC: 26253 AN: 33478

American (AMR) AF: 0.838 AC: 37497 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 21308 AN: 26134

East Asian (EAS) AF: 0.969 AC: 38456 AN: 39696

South Asian (SAS) AF: 0.903 AC: 77901 AN: 86256

European-Finnish (FIN) AF: 0.675 AC: 36054 AN: 53416

Middle Eastern (MID) AF: 0.882 AC: 5089 AN: 5768

European-Non Finnish (NFE) AF: 0.746 AC: 829553 AN: 1111956

Other (OTH) AF: 0.785 AC: 47388 AN: 60392

GnomAD4 genome AF: 0.780 AC: 118605 AN: 152054 Hom.: 46556 Cov.: 31 AF XY: 0.781 AC XY: 58029 AN XY: 74308

African (AFR) AF: 0.785 AC: 32555 AN: 41454

American (AMR) AF: 0.846 AC: 12931 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2860 AN: 3472

East Asian (EAS) AF: 0.955 AC: 4938 AN: 5170

South Asian (SAS) AF: 0.908 AC: 4384 AN: 4826

European-Finnish (FIN) AF: 0.657 AC: 6924 AN: 10536

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.755 AC: 51338 AN: 67994

Other (OTH) AF: 0.792 AC: 1674 AN: 2114

Alfa AF: 0.772 Hom.: 86289

Bravo AF: 0.794

Asia WGS AF: 0.872 AC: 3029 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	2	Exudative vitreoretinopathy 5 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	1.6
DANN	Benign	0.54
PhyloP100		-0.21
Mutation Taster		=97/3	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: rs41623; hg19: chr7-120428799; COSMIC: COSV108073906;