Variant 12-66153447-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_016056.4(TMBIM4):c.99C>T(p.Ala33=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,532,310 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 3 hom. )

Consequence

TMBIM4
NM_016056.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0001757

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.176

Variant links:

Genes affected

TMBIM4 (HGNC:24257): (transmembrane BAX inhibitor motif containing 4) Involved in negative regulation of apoptotic process and regulation of calcium-mediated signaling. Located in Golgi stack. [provided by Alliance of Genome Resources, Apr 2022]

TMBIM4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 12-66153447-G-A is Benign according to our data. Variant chr12-66153447-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2643165.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.176 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TMBIM4	NM_016056.4 linkuse as main transcript	c.99C>T	p.Ala33=	splice_region_variant, synonymous_variant	2/7	ENST00000358230.8
TMBIM4	NM_001282606.2 linkuse as main transcript	c.240C>T	p.Thr80=	splice_region_variant, synonymous_variant	3/8
TMBIM4	NM_001282609.2 linkuse as main transcript	c.99C>T	p.Ala33=	splice_region_variant, synonymous_variant	2/7
TMBIM4	NM_001282610.2 linkuse as main transcript	c.43-37C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMBIM4	ENST00000358230.8 linkuse as main transcript	c.99C>T	p.Ala33=	splice_region_variant, synonymous_variant	2/7	1	NM_016056.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00199

AC:

303

AN:

151978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00473

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00243

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00216

AC:

460

AN:

212708

Hom.:

AF XY:

0.00218

AC XY:

254

AN XY:

116756

show subpopulations

Gnomad AFR exome

AF:

0.000208

Gnomad AMR exome

AF:

0.000544

Gnomad ASJ exome

AF:

0.00196

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000298

Gnomad FIN exome

AF:

0.00503

Gnomad NFE exome

AF:

0.00298

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00252

AC:

3476

AN:

1380216

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

1676

AN XY:

689232

show subpopulations

Gnomad4 AFR exome

AF:

0.000234

Gnomad4 AMR exome

AF:

0.000834

Gnomad4 ASJ exome

AF:

0.00154

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000567

Gnomad4 FIN exome

AF:

0.00564

Gnomad4 NFE exome

AF:

0.00274

Gnomad4 OTH exome

AF:

0.00252

GnomAD4 genome

AF:

0.00199

AC:

303

AN:

152094

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

159

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.000723

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00473

Gnomad4 NFE

AF:

0.00243

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00203

Hom.:

Bravo

AF:

0.00205

Asia WGS

AF:

0.000579

AC:

AN:

3470

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

TMBIM4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00018

dbscSNV1_RF

Benign

0.0060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over