rs1726886

chr12-44328993-G-Achr12-44328993-G-T

Variant summary

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

The NM_032256.3(TMEM117):c.768+29254G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 151,112 control chromosomes in the GnomAD database, including 34,980 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 0.67 (34980 hom., cov: 27)
• Consequence: TMEM117 NM_032256.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262

Genes affected

TMEM117 (HGNC:25308): (transmembrane protein 117) Involved in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress. Located in endoplasmic reticulum and 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM117	NM_032256.3	c.768+29254G>A		intron_variant		ENST00000266534.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM117	ENST00000266534.8	c.768+29254G>A		intron_variant		1	NM_032256.3	P1

Frequencies

GnomAD3 genomes AF: 0.667 AC: 100651 AN: 150994 Hom.: 34921 Cov.: 27

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.667 AC: 100767 AN: 151112 Hom.: 34980 Cov.: 27 AF XY: 0.672 AC XY: 49556 AN XY: 73746

Gnomad4 AFR AF: 0.848

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.895

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.659

Alfa AF: 0.598 Hom.: 5833

Bravo AF: 0.687

Asia WGS AF: 0.788 AC: 2740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.9
Dann	Benign	0.46

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: rs1726886; hg19: chr12-44722776;