Variant chr2-218275565-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022152.6(TMBIM1):c.846C>G(p.Pro282Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,613,430 control chromosomes in the GnomAD database, including 125,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10013 hom., cov: 33)

Exomes 𝑓: 0.40 ( 115027 hom. )

Consequence

TMBIM1
NM_022152.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -9.03

Variant links:

Genes affected

TMBIM1 (HGNC:23410): (transmembrane BAX inhibitor motif containing 1) Enables death receptor binding activity. Involved in negative regulation of Fas signaling pathway; negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; and negative regulation of protein localization to plasma membrane. Located in Golgi apparatus; endosome membrane; and lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMBIM1 links:

PNKD (HGNC:9153): (PNKD metallo-beta-lactamase domain containing) This gene is thought to play a role in the regulation of myofibrillogenesis. Mutations in this gene have been associated with the movement disorder paroxysmal non-kinesigenic dyskinesia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

PNKD links:

TMBIM1 (HGNC:):

TMBIM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 2-218275565-G-C is Benign according to our data. Variant chr2-218275565-G-C is described in ClinVar as [Benign]. Clinvar id is 1264824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-9.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMBIM1	NM_022152.6 linkuse as main transcript	c.846C>G	p.Pro282Pro	synonymous_variant	12/12	ENST00000258412.8	NP_071435.2	Q969X1B3KSM0A0A024R472
PNKD	NM_015488.5 linkuse as main transcript	c.236+4016G>C		intron_variant		ENST00000273077.9	NP_056303.3	Q8N490-1A0A024R415

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMBIM1	ENST00000258412.8 linkuse as main transcript	c.846C>G	p.Pro282Pro	synonymous_variant	12/12	1	NM_022152.6	ENSP00000258412.3		Q969X1
PNKD	ENST00000273077.9 linkuse as main transcript	c.236+4016G>C		intron_variant		1	NM_015488.5	ENSP00000273077.4		Q8N490-1

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

54151

AN:

152008

Hom.:

10012

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.429

Gnomad AMR

AF:

0.432

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.396

Gnomad SAS

AF:

0.354

Gnomad FIN

AF:

0.285

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.405

Gnomad OTH

AF:

0.392

GnomAD3 exomes

AF:

0.384

AC:

96341

AN:

250646

Hom.:

18822

AF XY:

0.384

AC XY:

52052

AN XY:

135494

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.454

Gnomad ASJ exome

AF:

0.390

Gnomad EAS exome

AF:

0.386

Gnomad SAS exome

AF:

0.352

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.406

Gnomad OTH exome

AF:

0.409

GnomAD4 exome

AF:

0.395

AC:

577380

AN:

1461304

Hom.:

115027

Cov.:

AF XY:

0.394

AC XY:

286722

AN XY:

726950

show subpopulations

Gnomad4 AFR exome

AF:

0.247

Gnomad4 AMR exome

AF:

0.448

Gnomad4 ASJ exome

AF:

0.388

Gnomad4 EAS exome

AF:

0.388

Gnomad4 SAS exome

AF:

0.351

Gnomad4 FIN exome

AF:

0.302

Gnomad4 NFE exome

AF:

0.405

Gnomad4 OTH exome

AF:

0.396

GnomAD4 genome

AF:

0.356

AC:

54165

AN:

152126

Hom.:

10013

Cov.:

AF XY:

0.354

AC XY:

26337

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.255

Gnomad4 AMR

AF:

0.432

Gnomad4 ASJ

AF:

0.393

Gnomad4 EAS

AF:

0.395

Gnomad4 SAS

AF:

0.354

Gnomad4 FIN

AF:

0.285

Gnomad4 NFE

AF:

0.405

Gnomad4 OTH

AF:

0.392

Alfa

AF:

0.316

Hom.:

1406

Bravo

AF:

0.363

EpiCase

AF:

0.404

EpiControl

AF:

0.415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0090

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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