12-26992864-T-C

Variant names:

• chr12-26992864-T-C
• rs1552257
• NM_016551.3:c.691-2237A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016551.3(TM7SF3):​c.691-2237A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,222 control chromosomes in the GnomAD database, including 4,090 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4090 hom., cov: 30)
• Consequence: TM7SF3 NM_016551.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.667

Genes affected

TM7SF3 (HGNC:23049): (transmembrane 7 superfamily member 3) Involved in cellular response to unfolded protein; negative regulation of programmed cell death; and positive regulation of insulin secretion. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TM7SF3	NM_016551.3	c.691-2237A>G		intron_variant	Intron 5 of 11	ENST00000343028.9	NP_057635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TM7SF3	ENST00000343028.9	c.691-2237A>G		intron_variant	Intron 5 of 11	1	NM_016551.3	ENSP00000342322.4

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34227 AN: 151116 Hom.: 4087 Cov.: 30

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.216

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.226 AC: 34240 AN: 151222 Hom.: 4090 Cov.: 30 AF XY: 0.229 AC XY: 16886 AN XY: 73880

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.218

Alfa AF: 0.205 Hom.: 530

Bravo AF: 0.226

Asia WGS AF: 0.319 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.2
DANN	Benign	0.80

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: rs1552257; hg19: chr12-27145797;