12-44210324-A-G

Position:

• chr12-44210324-A-G

Variant summary

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

The NM_032256.3(TMEM117):​c.511-966A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,148 control chromosomes in the GnomAD database, including 926 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 0.10 (926 hom., cov: 32)
• Consequence: TMEM117 NM_032256.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM117	NM_032256.3	c.511-966A>G		intron_variant		ENST00000266534.8	NP_115632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM117	ENST00000266534.8	c.511-966A>G		intron_variant		1	NM_032256.3	ENSP00000266534	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15781 AN: 152030 Hom.: 925 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0747

Gnomad AMR AF: 0.0942

Gnomad ASJ AF: 0.0936

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0337

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.192

Gnomad NFE AF: 0.0866

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.104 AC: 15794 AN: 152148 Hom.: 926 Cov.: 32 AF XY: 0.102 AC XY: 7615 AN XY: 74386

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.0945

Gnomad4 ASJ AF: 0.0936

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0334

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0866

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0352 Hom.: 31

Bravo AF: 0.106

Asia WGS AF: 0.0260 AC: 91 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.79
DANN	Benign	0.61

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: rs10506241; hg19: chr12-44604107;