12-43904614-G-A

Variant names:

• chr12-43904614-G-A
• rs4488262
• NM_032256.3:c.278-39596G>A

Variant summary

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

The NM_032256.3(TMEM117):​c.278-39596G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.951 in 152,136 control chromosomes in the GnomAD database, including 68,898 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 0.95 (68898 hom., cov: 29)
• Consequence: TMEM117 NM_032256.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514

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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM117	NM_032256.3	c.278-39596G>A		intron_variant	Intron 2 of 7	ENST00000266534.8	NP_115632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM117	ENST00000266534.8	c.278-39596G>A		intron_variant	Intron 2 of 7	1	NM_032256.3	ENSP00000266534.3
TMEM117	ENST00000551577.5	c.278-39596G>A		intron_variant	Intron 2 of 6	1		ENSP00000448595.1
TMEM117	ENST00000546868.5	n.278-39596G>A		intron_variant	Intron 2 of 6	1		ENSP00000446952.1
TMEM117	ENST00000550495.1	c.-23+59686G>A		intron_variant	Intron 1 of 5	5		ENSP00000448657.2

Frequencies

GnomAD3 genomes AF: 0.951 AC: 144588 AN: 152018 Hom.: 68850 Cov.: 29

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.986

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.968

Gnomad OTH AF: 0.961

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

GnomAD4 genome AF: 0.951 AC: 144693 AN: 152136 Hom.: 68898 Cov.: 29 AF XY: 0.952 AC XY: 70814 AN XY: 74374

African (AFR) AF: 0.898 AC: 37242 AN: 41450

American (AMR) AF: 0.965 AC: 14739 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.986 AC: 3423 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5169 AN: 5170

South Asian (SAS) AF: 0.988 AC: 4760 AN: 4816

European-Finnish (FIN) AF: 0.972 AC: 10306 AN: 10600

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.968 AC: 65854 AN: 68026

Other (OTH) AF: 0.962 AC: 2035 AN: 2116

Alfa AF: 0.965 Hom.: 114201

Bravo AF: 0.949

Asia WGS AF: 0.987 AC: 3432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.31
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

Publications

LitVar

Other links and lift over

dbSNP: rs4488262; hg19: chr12-44298417;