chrX-153796423-C-T

Variant names:

• chrX-153796423-C-T
• rs781817133
• NM_006280.3:c.68-11C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006280.3(SSR4):​c.68-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000945 in 1,058,561 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: 25)
  • Exomes 𝑓: 9.4e-7 (0 hom. 0 hem.)
• Consequence: SSR4 NM_006280.3 intron
• Scores: Splicing: ADA: 0.00006647
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.452
• 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: 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=-0.86).
• BP6: Variant X-153796423-C-T is Benign according to our data. Variant chrX-153796423-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2879286.Status of the report is criteria_provided_single_submitter, 1 stars.

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.68-11C>T		intron	N/A	NP_006271.1	P51571
	SSR4	NM_001440795.1		c.149-11C>T		intron	N/A	NP_001427724.1
	SSR4	NM_001204526.2		c.101-11C>T		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.68-11C>T		intron	N/A	ENSP00000359103.3	P51571
	SSR4	ENST00000320857.7	TSL:2	c.68-11C>T		intron	N/A	ENSP00000317331.3	P51571
	SSR4	ENST00000370087.5	TSL:3	c.68-11C>T		intron	N/A	ENSP00000359104.1	P51571

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 9.45e-7 AC: 1 AN: 1058561 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 333299

African (AFR) AF: 0.0000390 AC: 1 AN: 25626

American (AMR) AF: 0.00 AC: 0 AN: 35111

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19080

East Asian (EAS) AF: 0.00 AC: 0 AN: 30034

South Asian (SAS) AF: 0.00 AC: 0 AN: 53209

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40031

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4043

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 806654

Other (OTH) AF: 0.00 AC: 0 AN: 44773

GnomAD4 genome Cov.: 25

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.76
PhyloP100		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000066
dbscSNV1_RF	Benign	0.0040
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: rs781817133; hg19: chrX-153061878;