Variant 17-21198467-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003876.3(TMEM11):c.436C>T(p.Leu146=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00142 in 1,614,216 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 16 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 10 hom. )

Consequence

TMEM11
NM_003876.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.36

Variant links:

Genes affected

TMEM11 (HGNC:16823): (transmembrane protein 11) Involved in mitochondrion organization. Located in mitochondrion. Is integral component of mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 17-21198467-G-A is Benign according to our data. Variant chr17-21198467-G-A is described in ClinVar as [Benign]. Clinvar id is 784738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00714 (1087/152322) while in subpopulation AFR AF= 0.0233 (970/41564). AF 95% confidence interval is 0.0221. There are 16 homozygotes in gnomad4. There are 499 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM11	NM_003876.3 linkuse as main transcript	c.436C>T	p.Leu146=	synonymous_variant	2/2	ENST00000317635.6	NP_003867.1
TMEM11	NR_024547.2 linkuse as main transcript	n.737C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TMEM11	ENST00000317635.6 linkuse as main transcript	c.436C>T	p.Leu146=	synonymous_variant	2/2	1	NM_003876.3	ENSP00000319992	P1
TMEM11	ENST00000577419.5 linkuse as main transcript	n.737C>T		non_coding_transcript_exon_variant	3/3	2
TMEM11	ENST00000583264.1 linkuse as main transcript	n.608C>T		non_coding_transcript_exon_variant	3/3	2
TMEM11	ENST00000584432.5 linkuse as main transcript	n.1135C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00710

AC:

1081

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0232

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.00209

AC:

526

AN:

251480

Hom.:

AF XY:

0.00153

AC XY:

208

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0241

Gnomad AMR exome

AF:

0.00228

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000343

Gnomad OTH exome

AF:

0.00195

GnomAD4 exome

AF:

0.000824

AC:

1205

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000733

AC XY:

533

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0222

Gnomad4 AMR exome

AF:

0.00228

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000174

Gnomad4 OTH exome

AF:

0.00237

GnomAD4 genome

AF:

0.00714

AC:

1087

AN:

152322

Hom.:

Cov.:

AF XY:

0.00670

AC XY:

499

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0233

Gnomad4 AMR

AF:

0.00503

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.00435

Hom.:

Bravo

AF:

0.00843

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000771

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.72

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