X-135967168-G-A

Position:

• chrX-135967168-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_173470.3(MMGT1):​c.236+222C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 111,266 control chromosomes in the GnomAD database, including 478 homozygotes. There are 3,310 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (478 hom., 3310 hem., cov: 23)
• Consequence: MMGT1 NM_173470.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.19

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant X-135967168-G-A is Benign according to our data. Variant chrX-135967168-G-A is described in ClinVar as [Benign]. Clinvar id is 1281705.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMGT1	NM_173470.3	c.236+222C>T		intron_variant		ENST00000305963.3
MMGT1	NM_001330000.2	c.236+222C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMGT1	ENST00000305963.3	c.236+222C>T		intron_variant		1	NM_173470.3	P1
MMGT1	ENST00000679621.1	c.236+222C>T		intron_variant				P1
MMGT1	ENST00000680510.2	c.*33+222C>T		intron_variant
MMGT1	ENST00000681201.1	c.133-1985C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.101 AC: 11189 AN: 111215 Hom.: 475 Cov.: 23 AF XY: 0.0990 AC XY: 3313 AN XY: 33457

Gnomad AFR AF: 0.0258

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0743

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.0844

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.100

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.101 AC: 11192 AN: 111266 Hom.: 478 Cov.: 23 AF XY: 0.0988 AC XY: 3310 AN XY: 33518

Gnomad4 AFR AF: 0.0257

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0745

Gnomad4 SAS AF: 0.0345

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.0996

Alfa AF: 0.122 Hom.: 1046

Bravo AF: 0.104

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.045
DANN	Benign	0.68

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: rs55994964; hg19: chrX-135049327;