NM_173470.3:c.-299G>C

Variant names:

• chrX-135973974-C-G
• rs3747460
• NM_173470.3:c.-299G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_173470.3(MMGT1):​c.-299G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 12)
• Consequence: MMGT1 NM_173470.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320
• Publications: 2 publications found

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]

SLC9A6 (HGNC:11079): (solute carrier family 9 member A6) This gene encodes a sodium-hydrogen exchanger that is amember of the solute carrier family 9. The encoded protein localizes to early and recycling endosomes and may be involved in regulating endosomal pH and volume. Defects in this gene are associated with X-linked syndromic cognitive disability, Christianson type. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]

SLC9A6 Gene-Disease associations (from GenCC):

• Christianson syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, G2P, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.01).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173470.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMGT1	NM_173470.3	MANE Select	c.-299G>C		5_prime_UTR	Exon 1 of 4	NP_775741.1	Q8N4V1-1
	SLC9A6	NM_001400909.1		c.-241C>G		5_prime_UTR	Exon 1 of 18	NP_001387838.1	Q92581-3
	MMGT1	NM_001330000.2		c.-222G>C		5_prime_UTR	Exon 1 of 5	NP_001316929.1	Q8N4V1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMGT1	ENST00000305963.3	TSL:1 MANE Select	c.-299G>C		5_prime_UTR	Exon 1 of 4	ENSP00000306220.2	Q8N4V1-1
	SLC9A6	ENST00000636347.1	TSL:5	c.-241C>G		5_prime_UTR	Exon 1 of 18	ENSP00000490648.1	Q92581-3
	MMGT1	ENST00000679621.1		c.-222G>C		5_prime_UTR	Exon 1 of 5	ENSP00000505226.1	Q8N4V1-1

Frequencies

GnomAD3 genomes Cov.: 12

GnomAD4 exome Cov.: 18

GnomAD4 genome Cov.: 12

Alfa AF: 0.00 Hom.: 1884

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.1
DANN	Benign	0.81
PhyloP100		-0.32
PromoterAI		-0.071	Neutral

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

Other links and lift over

dbSNP: rs3747460; hg19: chrX-135056133;