rs782262585

Variant names:

• chrX-153796429-C-T
• rs782262585
• NM_006280.3:c.68-5C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_006280.3(SSR4):​c.68-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,189,127 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000044 (0 hom., 3 hem., cov: 24)
  • Exomes 𝑓: 0.000012 (0 hom. 5 hem.)
• Consequence: SSR4 NM_006280.3 splice_region, intron
• Scores: Splicing: ADA: 0.00004804
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.501
• Publications: 0 publications found

Genes affected

SSR4 (HGNC:11326): (signal sequence receptor subunit 4) This gene encodes the delta subunit of the translocon-associated protein complex which is involved in translocating proteins across the endoplasmic reticulum membrane. The encoded protein is located in the Xq28 region and is arranged in a compact head-to-head manner with the isocitrate dehydrogenase 3 (NAD+) gamma gene and both genes are driven by a CpG-embedded bidirectional promoter. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2011]

SSR4 Gene-Disease associations (from GenCC):

• SSR4-congenital disorder of glycosylation

  Inheritance: XL Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant X-153796429-C-T is Benign according to our data. Variant chrX-153796429-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 515985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd4 at 3 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006280.3. 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
	SSR4	NM_006280.3	MANE Select	c.68-5C>T		splice_region intron	N/A	NP_006271.1	P51571
	SSR4	NM_001440795.1		c.149-5C>T		splice_region intron	N/A	NP_001427724.1
	SSR4	NM_001204526.2		c.101-5C>T		splice_region intron	N/A	NP_001191455.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSR4	ENST00000370086.8	TSL:1 MANE Select	c.68-5C>T		splice_region intron	N/A	ENSP00000359103.3	P51571
	SSR4	ENST00000320857.7	TSL:2	c.68-5C>T		splice_region intron	N/A	ENSP00000317331.3	P51571
	SSR4	ENST00000370087.5	TSL:3	c.68-5C>T		splice_region intron	N/A	ENSP00000359104.1	P51571

Frequencies

GnomAD3 genomes AF: 0.0000444 AC: 5 AN: 112535 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000935

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00108

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000220 AC: 4 AN: 181574 AF XY: 0.0000151

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000121 AC: 13 AN: 1076539 Hom.: 0 Cov.: 27 AF XY: 0.0000145 AC XY: 5 AN XY: 345889

African (AFR) AF: 0.00 AC: 0 AN: 25988

American (AMR) AF: 0.00 AC: 0 AN: 35137

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19190

East Asian (EAS) AF: 0.00 AC: 0 AN: 30131

South Asian (SAS) AF: 0.000168 AC: 9 AN: 53610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40119

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4082

European-Non Finnish (NFE) AF: 0.00000365 AC: 3 AN: 822885

Other (OTH) AF: 0.0000220 AC: 1 AN: 45397

GnomAD4 genome AF: 0.0000444 AC: 5 AN: 112588 Hom.: 0 Cov.: 24 AF XY: 0.0000863 AC XY: 3 AN XY: 34748

African (AFR) AF: 0.00 AC: 0 AN: 31049

American (AMR) AF: 0.0000934 AC: 1 AN: 10708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3594

South Asian (SAS) AF: 0.00109 AC: 3 AN: 2756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53216

Other (OTH) AF: 0.00 AC: 0 AN: 1533

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.64
DANN	Benign	0.70
PhyloP100		-0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000048
dbscSNV1_RF	Benign	0.012
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: rs782262585; hg19: chrX-153061884;