NM_006280.3:c.187-301_352-15del

Variant names:

• chrX-153797128-GGGCACCCCTGACCCCAGCACCTCCCTTGTAGACTCAGGAAATCACTCAGCCCTTTTGATCATCCCGCCCCTGCTCACAGTCAACAGGGTTCCTATGCGTCCAGTTAGGCCCGGCCATGGGGATCTGGCCTTGTGCCCCCGTAGGGAAGACCAATGCAGAGGGCCAGTCACGGGATTGGTGAGTGTTACTTGGTACCTCCTGCCAGGGACACTGCAGCCCCCAACTGGGCCTAGCCTGCCCACCTGCAGGCCGTGTGAGCAGCGCACAGGGCTCCTCTGCCCACACCCAGAGGGGGCAGAAGGTGACCCTGCCTTTGTTCCCTCACCCAGAACATGGCTCTCTATGCTGACGTCGGTGGAAAACAATTCCCTGTCACTCGAGGCCAGGATGTGGGGCGTTATCAGGTGAGGGGCCAATGGTTCCCTTGCTAGGGGGCTCCCTGCTCCCGGGTGTGACCTGAAGCCCCAGGGGTGGCCGGTCAACCAGGGCCAGGGGCCGTGGGCTCTGGCTGCCGGAGTGCTGCAGTGTCGGCACTGGTGGTCAGGGTGGCCCCTCCGTGTCCACTCTGCCCACACTCTGCTCAACACCCAACCCAGGTGTCCTGGAGCCTGGACCACAAGAGCGCCCACGCAGGCACCTATGAGGTTAGATTCTTCGACGAGGAGTCCTACAGCCTCCTCAGGAAGGTGAGGACTCCTGTAGCCCACTGTGCTCCCCTGTCCCTGGGGAGCAGGATGGGCTGGGTTGGGAGGTGCTGGCAGCAAGTCCTGAGCTGGGTGGCCTTTCTGTGATCCTGTCCCTTCCTCAGTGTCTCTTGCCCATTTCTCTCCTTTCCTTTTCTGGGGCTTGGGCCGGTGTTCCTACCTGTCTTTCCCCTCCCCTCCCCACCCCCACACGCCA-G
• rs1557072752
• NM_006280.3:c.187-301_352-15del

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP5

The NM_006280.3(SSR4):​c.187-301_352-15del variant causes a exon loss change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 24)
• Consequence: SSR4 NM_006280.3 exon_loss
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.06
• 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP5: Variant X-153797128-GGGCACCCCTGACCCCAGCACCTCCCTTGTAGACTCAGGAAATCACTCAGCCCTTTTGATCATCCCGCCCCTGCTCACAGTCAACAGGGTTCCTATGCGTCCAGTTAGGCCCGGCCATGGGGATCTGGCCTTGTGCCCCCGTAGGGAAGACCAATGCAGAGGGCCAGTCACGGGATTGGTGAGTGTTACTTGGTACCTCCTGCCAGGGACACTGCAGCCCCCAACTGGGCCTAGCCTGCCCACCTGCAGGCCGTGTGAGCAGCGCACAGGGCTCCTCTGCCCACACCCAGAGGGGGCAGAAGGTGACCCTGCCTTTGTTCCCTCACCCAGAACATGGCTCTCTATGCTGACGTCGGTGGAAAACAATTCCCTGTCACTCGAGGCCAGGATGTGGGGCGTTATCAGGTGAGGGGCCAATGGTTCCCTTGCTAGGGGGCTCCCTGCTCCCGGGTGTGACCTGAAGCCCCAGGGGTGGCCGGTCAACCAGGGCCAGGGGCCGTGGGCTCTGGCTGCCGGAGTGCTGCAGTGTCGGCACTGGTGGTCAGGGTGGCCCCTCCGTGTCCACTCTGCCCACACTCTGCTCAACACCCAACCCAGGTGTCCTGGAGCCTGGACCACAAGAGCGCCCACGCAGGCACCTATGAGGTTAGATTCTTCGACGAGGAGTCCTACAGCCTCCTCAGGAAGGTGAGGACTCCTGTAGCCCACTGTGCTCCCCTGTCCCTGGGGAGCAGGATGGGCTGGGTTGGGAGGTGCTGGCAGCAAGTCCTGAGCTGGGTGGCCTTTCTGTGATCCTGTCCCTTCCTCAGTGTCTCTTGCCCATTTCTCTCCTTTCCTTTTCTGGGGCTTGGGCCGGTGTTCCTACCTGTCTTTCCCCTCCCCTCCCCACCCCCACACGCCA-G is Pathogenic according to our data. Variant chrX-153797128-GGGCACCCCTGACCCCAGCACCTCCCTTGTAGACTCAGGAAATCACTCAGCCCTTTTGATCATCCCGCCCCTGCTCACAGTCAACAGGGTTCCTATGCGTCCAGTTAGGCCCGGCCATGGGGATCTGGCCTTGTGCCCCCGTAGGGAAGACCAATGCAGAGGGCCAGTCACGGGATTGGTGAGTGTTACTTGGTACCTCCTGCCAGGGACACTGCAGCCCCCAACTGGGCCTAGCCTGCCCACCTGCAGGCCGTGTGAGCAGCGCACAGGGCTCCTCTGCCCACACCCAGAGGGGGCAGAAGGTGACCCTGCCTTTGTTCCCTCACCCAGAACATGGCTCTCTATGCTGACGTCGGTGGAAAACAATTCCCTGTCACTCGAGGCCAGGATGTGGGGCGTTATCAGGTGAGGGGCCAATGGTTCCCTTGCTAGGGGGCTCCCTGCTCCCGGGTGTGACCTGAAGCCCCAGGGGTGGCCGGTCAACCAGGGCCAGGGGCCGTGGGCTCTGGCTGCCGGAGTGCTGCAGTGTCGGCACTGGTGGTCAGGGTGGCCCCTCCGTGTCCACTCTGCCCACACTCTGCTCAACACCCAACCCAGGTGTCCTGGAGCCTGGACCACAAGAGCGCCCACGCAGGCACCTATGAGGTTAGATTCTTCGACGAGGAGTCCTACAGCCTCCTCAGGAAGGTGAGGACTCCTGTAGCCCACTGTGCTCCCCTGTCCCTGGGGAGCAGGATGGGCTGGGTTGGGAGGTGCTGGCAGCAAGTCCTGAGCTGGGTGGCCTTTCTGTGATCCTGTCCCTTCCTCAGTGTCTCTTGCCCATTTCTCTCCTTTCCTTTTCTGGGGCTTGGGCCGGTGTTCCTACCTGTCTTTCCCCTCCCCTCCCCACCCCCACACGCCA-G is described in ClinVar as Pathogenic. ClinVar VariationId is 372143.Status of the report is no_assertion_criteria_provided, 0 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSR4	NM_006280.3	MANE Select	c.187-301_352-15del		exon_loss	Exon 3 of 6	NP_006271.1
	SSR4	NM_006280.3	MANE Select	c.187-301_352-15del		exon_loss	Exon 4 of 6	NP_006271.1
	SSR4	NM_001440795.1		c.268-301_433-15del		exon_loss	Exon 4 of 7	NP_001427724.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSR4	ENST00000370086.8	TSL:1 MANE Select	c.187-329_352-43del		exon_loss	Exon 3 of 6	ENSP00000359103.3
	SSR4	ENST00000370086.8	TSL:1 MANE Select	c.187-329_352-43del		exon_loss	Exon 4 of 6	ENSP00000359103.3
	SSR4	ENST00000320857.7	TSL:2	c.187-329_352-43del		exon_loss	Exon 4 of 7	ENSP00000317331.3

Frequencies

GnomAD3 genomes Cov.: 24

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 24

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

SSR4-congenital disorder of glycosylation Pathogenic:1

Nov 28, 2016

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

Splicing

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

Other links and lift over

dbSNP: rs1557072752; hg19: chrX-153062583;