rs3747460

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-135973974-C-T
• chrX-135973974-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001400909.1(SLC9A6):​c.-241C>T variant causes a 5 prime UTR premature start codon gain 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 0.027 (33 hom., 294 hem., cov: 12)
  • Exomes 𝑓: 0.035 (430 hom. 10728 hem.)
• Consequence: SLC9A6 NM_001400909.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.012).
• BP6: Variant X-135973974-C-T is Benign according to our data. Variant chrX-135973974-C-T is described in ClinVar as Benign. ClinVar VariationId is 1277542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001400909.1. 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>A		5_prime_UTR	Exon 1 of 4	NP_775741.1	Q8N4V1-1
	SLC9A6	NM_001400909.1		c.-241C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	NP_001387838.1	Q92581-3
	SLC9A6	NM_001400909.1		c.-241C>T		5_prime_UTR	Exon 1 of 18	NP_001387838.1	Q92581-3

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.0272 AC: 2218 AN: 81519 Hom.: 33 Cov.: 12

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.0251

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.0534

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0302

Gnomad MID AF: 0.0217

Gnomad NFE AF: 0.0272

Gnomad OTH AF: 0.0154

GnomAD2 exomes AF: 0.0350 AC: 3810 AN: 108776 AF XY: 0.0421

Gnomad AFR exome AF: 0.0267

Gnomad AMR exome AF: 0.00750

Gnomad ASJ exome AF: 0.0228

Gnomad EAS exome AF: 0.0440

Gnomad FIN exome AF: 0.0301

Gnomad NFE exome AF: 0.0281

Gnomad OTH exome AF: 0.0297

GnomAD4 exome AF: 0.0348 AC: 32315 AN: 927335 Hom.: 430 Cov.: 18 AF XY: 0.0402 AC XY: 10728 AN XY: 266827

African (AFR) AF: 0.0264 AC: 579 AN: 21922

American (AMR) AF: 0.00831 AC: 209 AN: 25159

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 387 AN: 15422

East Asian (EAS) AF: 0.0542 AC: 1018 AN: 18791

South Asian (SAS) AF: 0.104 AC: 4929 AN: 47597

European-Finnish (FIN) AF: 0.0344 AC: 968 AN: 28153

Middle Eastern (MID) AF: 0.0170 AC: 60 AN: 3528

European-Non Finnish (NFE) AF: 0.0314 AC: 22917 AN: 729231

Other (OTH) AF: 0.0333 AC: 1248 AN: 37532

GnomAD4 genome AF: 0.0272 AC: 2218 AN: 81520 Hom.: 33 Cov.: 12 AF XY: 0.0228 AC XY: 294 AN XY: 12870

African (AFR) AF: 0.0236 AC: 488 AN: 20649

American (AMR) AF: 0.0122 AC: 83 AN: 6819

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 50 AN: 2142

East Asian (EAS) AF: 0.0533 AC: 138 AN: 2590

South Asian (SAS) AF: 0.119 AC: 157 AN: 1319

European-Finnish (FIN) AF: 0.0302 AC: 96 AN: 3180

Middle Eastern (MID) AF: 0.0185 AC: 3 AN: 162

European-Non Finnish (NFE) AF: 0.0272 AC: 1173 AN: 43085

Other (OTH) AF: 0.0161 AC: 17 AN: 1057

Alfa AF: 0.0262 Hom.: 1884

Bravo AF: 0.0259

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.2
DANN	Benign	0.90
PhyloP100		-0.32
PromoterAI		-0.055	Neutral
Mutation Taster		=294/6	polymorphism (auto)

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; COSMIC: COSV107374976; COSMIC: COSV107374976;