X-135973535-T-C

Position:

• chrX-135973535-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_173470.3(MMGT1):​c.79+62A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (26303 hom., 27465 hem., cov: 23)
  • Exomes 𝑓: 0.84 (210070 hom. 205072 hem.)
  • Failed GnomAD Quality Control
• Consequence: MMGT1 NM_173470.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.308

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant X-135973535-T-C is Benign according to our data. Variant chrX-135973535-T-C is described in ClinVar as [Benign]. Clinvar id is 1286341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMGT1	NM_173470.3	c.79+62A>G		intron_variant		ENST00000305963.3
MMGT1	NM_001330000.2	c.79+62A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMGT1	ENST00000305963.3	c.79+62A>G		intron_variant		1	NM_173470.3	P1
MMGT1	ENST00000679621.1	c.79+62A>G		intron_variant				P1
MMGT1	ENST00000680510.2	c.79+62A>G		intron_variant
MMGT1	ENST00000681201.1	c.79+62A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.822 AC: 91383 AN: 111217 Hom.: 26313 Cov.: 23 AF XY: 0.820 AC XY: 27420 AN XY: 33425

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.890

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.848

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.835 AC: 709862 AN: 849692 Hom.: 210070 AF XY: 0.846 AC XY: 205072 AN XY: 242526

Gnomad4 AFR exome AF: 0.784

Gnomad4 AMR exome AF: 0.783

Gnomad4 ASJ exome AF: 0.859

Gnomad4 EAS exome AF: 0.876

Gnomad4 SAS exome AF: 0.861

Gnomad4 FIN exome AF: 0.813

Gnomad4 NFE exome AF: 0.836

Gnomad4 OTH exome AF: 0.844

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.822 AC: 91410 AN: 111269 Hom.: 26303 Cov.: 23 AF XY: 0.820 AC XY: 27465 AN XY: 33487

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.817

Gnomad4 ASJ AF: 0.864

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.839

Gnomad4 FIN AF: 0.814

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.849

Alfa AF: 0.834 Hom.: 59267

Bravo AF: 0.817

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs6635201; hg19: chrX-135055694;