rs10506244

Positions:

• chr12-44322745-A-C

Variant summary

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

The NM_032256.3(TMEM117):​c.768+23006A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.048 in 152,226 control chromosomes in the GnomAD database, including 363 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 0.048 (363 hom., cov: 32)
• Consequence: TMEM117 NM_032256.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255

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 = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM117	NM_032256.3	c.768+23006A>C		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+23006A>C		intron_variant		1	NM_032256.3	ENSP00000266534.3

Frequencies

GnomAD3 genomes AF: 0.0479 AC: 7293 AN: 152108 Hom.: 361 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0185

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0480 AC: 7311 AN: 152226 Hom.: 363 Cov.: 32 AF XY: 0.0467 AC XY: 3477 AN XY: 74438

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0225

Gnomad4 ASJ AF: 0.0357

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0290

Gnomad4 FIN AF: 0.0146

Gnomad4 NFE AF: 0.0185

Gnomad4 OTH AF: 0.0412

Alfa AF: 0.0246 Hom.: 91

Bravo AF: 0.0510

Asia WGS AF: 0.0230 AC: 80 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	5.1
DANN	Benign	0.76

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: rs10506244; hg19: chr12-44716528;