Variant X-135965109-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_173470.3(MMGT1):c.311C>T(p.Ser104Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,205,221 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 72 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000090 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.00019 ( 0 hom. 69 hem. )

Consequence

MMGT1
NM_173470.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.52

Variant links:

Genes affected

MMGT1 (HGNC:28100): (membrane magnesium transporter 1) Contributes to membrane insertase activity. Involved in protein insertion into ER membrane by stop-transfer membrane-anchor sequence and tail-anchored membrane protein insertion into ER membrane. Is integral component of endoplasmic reticulum membrane. Part of EMC complex. [provided by Alliance of Genome Resources, Apr 2022]

MMGT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14745992).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMGT1	NM_173470.3 link	c.311C>T	p.Ser104Leu	missense_variant	4/4	ENST00000305963.3	NP_775741.1	Q8N4V1-1
MMGT1	NM_001330000.2 link	c.311C>T	p.Ser104Leu	missense_variant	5/5		NP_001316929.1	Q8N4V1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MMGT1	ENST00000305963.3 link	c.311C>T	p.Ser104Leu	missense_variant	4/4	1	NM_173470.3	ENSP00000306220.2	Q8N4V1-1
MMGT1	ENST00000679621.1 link	c.311C>T	p.Ser104Leu	missense_variant	5/5			ENSP00000505226.1	Q8N4V1-1
MMGT1	ENST00000680510 link	c.*108C>T		3_prime_UTR_variant	3/3			ENSP00000505521.1	A0A7P0T9E6
MMGT1	ENST00000681201 link	c.*66C>T		3_prime_UTR_variant	3/3			ENSP00000506673.1	A0A7P0TBL5

Frequencies

GnomAD3 genomes

AF:

0.0000897

AC:

AN:

111529

Hom.:

Cov.:

AF XY:

0.0000890

AC XY:

AN XY:

33709

show subpopulations

Gnomad AFR

AF:

0.0000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000115

AC:

AN:

182577

Hom.:

AF XY:

0.000134

AC XY:

AN XY:

67359

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.000328

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000136

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000188

AC:

206

AN:

1093692

Hom.:

Cov.:

AF XY:

0.000192

AC XY:

AN XY:

359146

show subpopulations

Gnomad4 AFR exome

AF:

0.0000760

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000221

Gnomad4 OTH exome

AF:

0.000174

GnomAD4 genome

AF:

0.0000897

AC:

AN:

111529

Hom.:

Cov.:

AF XY:

0.0000890

AC XY:

AN XY:

33709

show subpopulations

Gnomad4 AFR

AF:

0.0000652

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000150

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000209

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2024

The c.311C>T (p.S104L) alteration is located in exon 4 (coding exon 4) of the MMGT1 gene. This alteration results from a C to T substitution at nucleotide position 311, causing the serine (S) at amino acid position 104 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.080

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.9

REVEL

Benign

0.11

Sift

Benign

0.31

Sift4G

Benign

0.66

Polyphen

0.55

Vest4

0.16

MVP

0.63

MPC

1.0

ClinPred

0.20

GERP RS

4.8

Varity_R

0.31

gMVP

0.29

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