Variant 17-28357826-A-G 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_152464.3(TMEM199):c.156A>G(p.Gln52=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,614,070 control chromosomes in the GnomAD database, including 120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 29 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 91 hom. )

Consequence

TMEM199
NM_152464.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.545

Variant links:

Genes affected

TMEM199 (HGNC:18085): (transmembrane protein 199) The protein encoded by this gene has been observed to localize to the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) and coat protein complex I (COPI) in some human cells. The encoded protein shares some homology with the yeast protein Vma12. Defects in this gene are a cause of congenital disorder of glycosylation, type IIp. [provided by RefSeq, Mar 2016]

TMEM199 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=-0.57).

BP6

Variant 17-28357826-A-G is Benign according to our data. Variant chr17-28357826-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 773876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.545 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM199	NM_152464.3 linkuse as main transcript	c.156A>G	p.Gln52=	synonymous_variant	1/6	ENST00000292114.8	NP_689677.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM199	ENST00000292114.8 linkuse as main transcript	c.156A>G	p.Gln52=	synonymous_variant	1/6	1	NM_152464.3	ENSP00000292114	P1

Frequencies

GnomAD3 genomes

AF:

0.00369

AC:

562

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0815

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00661

AC:

1644

AN:

248806

Hom.:

AF XY:

0.00611

AC XY:

823

AN XY:

134778

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.0804

Gnomad SAS exome

AF:

0.00219

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000171

Gnomad OTH exome

AF:

0.00507

GnomAD4 exome

AF:

0.00188

AC:

2752

AN:

1461774

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

1328

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00214

Gnomad4 EAS exome

AF:

0.0432

Gnomad4 SAS exome

AF:

0.00272

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000166

Gnomad4 OTH exome

AF:

0.00853

GnomAD4 genome

AF:

0.00370

AC:

564

AN:

152296

Hom.:

Cov.:

AF XY:

0.00404

AC XY:

301

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.0817

Gnomad4 SAS

AF:

0.00808

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.000614

Hom.:

Bravo

AF:

0.00337

Asia WGS

AF:

0.0520

AC:

181

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 10, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -

TMEM199-CDG

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.2

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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