chr12-26992864-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016551.3. 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
	TM7SF3	NM_016551.3	MANE Select	c.691-2237A>G		intron	N/A	NP_057635.1	Q9NS93

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TM7SF3	ENST00000343028.9	TSL:1 MANE Select	c.691-2237A>G		intron	N/A	ENSP00000342322.4	Q9NS93
	TM7SF3	ENST00000867962.1		c.781-2237A>G		intron	N/A	ENSP00000538021.1
	TM7SF3	ENST00000867963.1		c.781-2237A>G		intron	N/A	ENSP00000538022.1

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

African (AFR) AF: 0.269 AC: 11048 AN: 41122

American (AMR) AF: 0.206 AC: 3130 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3464

East Asian (EAS) AF: 0.380 AC: 1948 AN: 5124

South Asian (SAS) AF: 0.290 AC: 1393 AN: 4802

European-Finnish (FIN) AF: 0.238 AC: 2460 AN: 10332

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.189 AC: 12836 AN: 67900

Other (OTH) AF: 0.218 AC: 456 AN: 2096

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.2
DANN	Benign	0.80
PhyloP100		0.67
Mutation Taster		=100/0	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: rs1552257; hg19: chr12-27145797;