rs10506243

Positions:

• chr12-44322027-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.768+22288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 152,334 control chromosomes in the GnomAD database, including 98 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 0.028 (98 hom., cov: 32)
• Consequence: TMEM117 NM_032256.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176

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]

LOC124902922 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM117	NM_032256.3	c.768+22288A>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.768+22288A>G		intron_variant		1	NM_032256.3	ENSP00000266534.3

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 4254 AN: 152216 Hom.: 99 Cov.: 32

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0182

Gnomad OTH AF: 0.0263

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

GnomAD4 genome AF: 0.0280 AC: 4258 AN: 152334 Hom.: 98 Cov.: 32 AF XY: 0.0269 AC XY: 2005 AN XY: 74492

Gnomad4 AFR AF: 0.0554

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.0357

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0228

Gnomad4 FIN AF: 0.0146

Gnomad4 NFE AF: 0.0181

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0211 Hom.: 18

Bravo AF: 0.0290

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.71

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: rs10506243; hg19: chr12-44715810;