Genetic Variant TMEM117:c.278-39596G>A (chr12-43904614-G-A) – ACMG Classification: Benign (-12 pts)

Germline classification Cancer classification (beta)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BA1BP4_Strong

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 cumulative frequency of 0.951 (AC=144,693) in the gnomAD database across 152,136 control chromosomes, including 68,898 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.977. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.514

Publications

3 publications found

Variant links:

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]

TMEM117 links:

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new If you want to explore the variant's impact on the transcript NM_032256.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.9770 — exceeds 5%% threshold (BA1 applied)

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMEM117	NM_032256.3	MANE Select	c.278-39596G>A	intron	N/A	NP_115632.1	Q9H0C3
TMEM117	NM_001286212.2		c.66-39596G>A	intron	N/A	NP_001273141.1
TMEM117	NM_001286213.2		c.-23+59686G>A	intron	N/A	NP_001273142.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMEM117	ENST00000266534.8	TSL:1 MANE Select	c.278-39596G>A	intron	N/A	ENSP00000266534.3	Q9H0C3
TMEM117	ENST00000551577.5	TSL:1	c.278-39596G>A	intron	N/A	ENSP00000448595.1	F8VS00
TMEM117	ENST00000546868.5	TSL:1	n.278-39596G>A	intron	N/A	ENSP00000446952.1	F8W1J2

Frequencies

GnomAD3 genomes

AF:

0.951

AC:

144588

AN:

152018

Hom.:

68850

Cov.:

show subpopulations

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.:

AF XY:

0.952

AC XY:

70814

AN XY:

74374

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

357

714

1071

1428

1785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.965

Hom.:

114201

Bravo

AF:

0.949

Asia WGS

AF:

0.987

AC:

3432

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

1.00

AC:

122838

AN:

122840

Turkish Variome

AF:

0.964

AC:

1491

AN:

1546

Hom.:

719

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.999

AC:

8955

AN:

8960

Hom.:

4475

ABraOM SABE-WGS-1171

AF:

0.947

AC:

2216

AN:

2340

Hom.:

1050

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.48

(source)

DANN

Benign

0.31

PhyloP100

-0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over