Variant 8-124314064-AAG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The ENST00000297632.8(TMEM65):c.622-5_622-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00385 in 1,608,138 control chromosomes in the GnomAD database, including 18 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 18 hom. )

Consequence

TMEM65
ENST00000297632.8 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.12

Variant links:

Genes affected

TMEM65 (HGNC:25203): (transmembrane protein 65) Predicted to be involved in cardiac ventricle development and regulation of cardiac conduction. Located in intercalated disc; mitochondrial inner membrane; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM65 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 8-124314064-AAG-A is Benign according to our data. Variant chr8-124314064-AAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 1175787.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM65	NM_194291.3 linkuse as main transcript	c.622-5_622-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000297632.8	NP_919267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM65	ENST00000297632.8 linkuse as main transcript	c.622-5_622-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_194291.3	ENSP00000297632	P1

Frequencies

GnomAD3 genomes

AF:

0.00314

AC:

478

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00197

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00532

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00274

AC:

674

AN:

245638

Hom.:

AF XY:

0.00284

AC XY:

378

AN XY:

133028

show subpopulations

Gnomad AFR exome

AF:

0.000621

Gnomad AMR exome

AF:

0.00289

Gnomad ASJ exome

AF:

0.00260

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000635

Gnomad FIN exome

AF:

0.00157

Gnomad NFE exome

AF:

0.00425

Gnomad OTH exome

AF:

0.00331

GnomAD4 exome

AF:

0.00393

AC:

5721

AN:

1455878

Hom.:

AF XY:

0.00392

AC XY:

2841

AN XY:

724548

show subpopulations

Gnomad4 AFR exome

AF:

0.000785

Gnomad4 AMR exome

AF:

0.00286

Gnomad4 ASJ exome

AF:

0.00334

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000526

Gnomad4 FIN exome

AF:

0.00202

Gnomad4 NFE exome

AF:

0.00457

Gnomad4 OTH exome

AF:

0.00422

GnomAD4 genome

AF:

0.00313

AC:

477

AN:

152260

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

222

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00531

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00407

Hom.:

Bravo

AF:

0.00301

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00464

EpiControl

AF:

0.00551

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

Jun 01, 2024

TMEM65: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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