Genetic Variant NM_001379110.1:c.-73G>A (chrX-135985461-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001379110.1(SLC9A6):c.-73G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000114 in 880,143 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000011 ( 0 hom. 1 hem. )

Consequence

SLC9A6
NM_001379110.1 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0970

Publications

0 publications found

Variant links:

Genes affected

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

SLC9A6 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant X-135985461-G-A is Benign according to our data. Variant chrX-135985461-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 506766.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379110.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC9A6	NM_001379110.1	MANE Select	c.-73G>A	5_prime_UTR	Exon 1 of 18	NP_001366039.1	A0A0D9SGH0
SLC9A6	NM_001438742.1		c.-42G>A	5_prime_UTR	Exon 1 of 17	NP_001425671.1
SLC9A6	NM_001042537.2		c.-42G>A	5_prime_UTR	Exon 1 of 16	NP_001036002.1	Q92581-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC9A6	ENST00000630721.3	TSL:4 MANE Select	c.-73G>A	5_prime_UTR	Exon 1 of 18	ENSP00000487486.2	A0A0D9SGH0
SLC9A6	ENST00000370695.8	TSL:1	c.-42G>A	5_prime_UTR	Exon 1 of 16	ENSP00000359729.4	Q92581-2
SLC9A6	ENST00000370698.7	TSL:1	c.-42G>A	5_prime_UTR	Exon 1 of 16	ENSP00000359732.3	Q92581-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000114

AC:

AN:

880143

Hom.:

Cov.:

AF XY:

0.00000394

AC XY:

AN XY:

254091

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17691

American (AMR)

AF:

0.00

AC:

AN:

10387

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12255

East Asian (EAS)

AF:

0.00

AC:

AN:

22295

South Asian (SAS)

AF:

0.00

AC:

AN:

33871

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22683

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2258

European-Non Finnish (NFE)

AF:

0.00000139

AC:

AN:

721336

Other (OTH)

AF:

0.00

AC:

AN:

37367

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

-0.097

PromoterAI

0.014

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over