12-43888363-A-G

Variant names:

• chr12-43888363-A-G
• rs2614394
• NM_032256.3:c.277+43435A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032256.3(TMEM117):​c.277+43435A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,012 control chromosomes in the GnomAD database, including 49,074 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 0.78 (49074 hom., cov: 30)
• Consequence: TMEM117 NM_032256.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.503
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032256.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM117	NM_032256.3	MANE Select	c.277+43435A>G		intron	N/A	NP_115632.1
	TMEM117	NM_001286212.2		c.65+43435A>G		intron	N/A	NP_001273141.1
	TMEM117	NM_001286213.2		c.-23+43435A>G		intron	N/A	NP_001273142.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM117	ENST00000266534.8	TSL:1 MANE Select	c.277+43435A>G		intron	N/A	ENSP00000266534.3
	TMEM117	ENST00000551577.5	TSL:1	c.277+43435A>G		intron	N/A	ENSP00000448595.1
	TMEM117	ENST00000546868.5	TSL:1	n.277+43435A>G		intron	N/A	ENSP00000446952.1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118935 AN: 151894 Hom.: 49050 Cov.: 30

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.902

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.818

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.783 AC: 119003 AN: 152012 Hom.: 49074 Cov.: 30 AF XY: 0.786 AC XY: 58428 AN XY: 74312

African (AFR) AF: 0.497 AC: 20589 AN: 41390

American (AMR) AF: 0.844 AC: 12899 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.902 AC: 3131 AN: 3472

East Asian (EAS) AF: 0.868 AC: 4479 AN: 5158

South Asian (SAS) AF: 0.845 AC: 4073 AN: 4818

European-Finnish (FIN) AF: 0.919 AC: 9716 AN: 10578

Middle Eastern (MID) AF: 0.815 AC: 238 AN: 292

European-Non Finnish (NFE) AF: 0.902 AC: 61315 AN: 67998

Other (OTH) AF: 0.818 AC: 1725 AN: 2108

Alfa AF: 0.852 Hom.: 17870

Bravo AF: 0.767

Asia WGS AF: 0.847 AC: 2946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.029
DANN	Benign	0.36
PhyloP100		-0.50
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: rs2614394; hg19: chr12-44282166;