Genetic Variant SSR4:c.187-301_352-15del (chrX-153797128-GGGCACCCCTGACCCCAGCACCTCCCTTGTAGACTCAGGAAATCACTCAGCCCTTTTGATCATCCCGCCCCTGCTCACAGTCAACAGGGTTCCTATGCGTCCAGTTAGGCCCGGCCATGGGGATCTGGCCTTGTGCCCCCGTAGGGAAGACCAATGCAGAGGGCCAGTCACGGGATTGGTGAGTGTTACTTGGTACCTCCTGCCAGGGACACTGCAGCCCCCAACTGGGCCTAGCCTGCCCACCTGCAGGCCGTGTGAGCAGCGCACAGGGCTCCTCTGCCCACACCCAGAGGGGGCAGAAGGTGACCCTGCCTTTGTTCCCTCACCCAGAACATGGCTCTCTATGCTGACGTCGGTGGAAAACAATTCCCTGTCACTCGAGGCCAGGATGTGGGGCGTTATCAGGTGAGGGGCCAATGGTTCCCTTGCTAGGGGGCTCCCTGCTCCCGGGTGTGACCTGAAGCCCCAGGGGTGGCCGGTCAACCAGGGCCAGGGGCCGTGGGCTCTGGCTGCCGGAGTGCTGCAGTGTCGGCACTGGTGGTCAGGGTGGCCCCTCCGTGTCCACTCTGCCCACACTCTGCTCAACACCCAACCCAGGTGTCCTGGAGCCTGGACCACAAGAGCGCCCACGCAGGCACCTATGAGGTTAGATTCTTCGACGAGGAGTCCTACAGCCTCCTCAGGAAGGTGAGGACTCCTGTAGCCCACTGTGCTCCCCTGTCCCTGGGGAGCAGGATGGGCTGGGTTGGGAGGTGCTGGCAGCAAGTCCTGAGCTGGGTGGCCTTTCTGTGATCCTGTCCCTTCCTCAGTGTCTCTTGCCCATTTCTCTCCTTTCCTTTTCTGGGGCTTGGGCCGGTGTTCCTACCTGTCTTTCCCCTCCCCTCCCCACCCCCACACGCCA-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

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. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 24)

Consequence

SSR4
NM_006280.3 exon_loss

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.06

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant X-153797128-GGGCACCCCTGACCCCAGCACCTCCCTTGTAGACTCAGGAAATCACTCAGCCCTTTTGATCATCCCGCCCCTGCTCACAGTCAACAGGGTTCCTATGCGTCCAGTTAGGCCCGGCCATGGGGATCTGGCCTTGTGCCCCCGTAGGGAAGACCAATGCAGAGGGCCAGTCACGGGATTGGTGAGTGTTACTTGGTACCTCCTGCCAGGGACACTGCAGCCCCCAACTGGGCCTAGCCTGCCCACCTGCAGGCCGTGTGAGCAGCGCACAGGGCTCCTCTGCCCACACCCAGAGGGGGCAGAAGGTGACCCTGCCTTTGTTCCCTCACCCAGAACATGGCTCTCTATGCTGACGTCGGTGGAAAACAATTCCCTGTCACTCGAGGCCAGGATGTGGGGCGTTATCAGGTGAGGGGCCAATGGTTCCCTTGCTAGGGGGCTCCCTGCTCCCGGGTGTGACCTGAAGCCCCAGGGGTGGCCGGTCAACCAGGGCCAGGGGCCGTGGGCTCTGGCTGCCGGAGTGCTGCAGTGTCGGCACTGGTGGTCAGGGTGGCCCCTCCGTGTCCACTCTGCCCACACTCTGCTCAACACCCAACCCAGGTGTCCTGGAGCCTGGACCACAAGAGCGCCCACGCAGGCACCTATGAGGTTAGATTCTTCGACGAGGAGTCCTACAGCCTCCTCAGGAAGGTGAGGACTCCTGTAGCCCACTGTGCTCCCCTGTCCCTGGGGAGCAGGATGGGCTGGGTTGGGAGGTGCTGGCAGCAAGTCCTGAGCTGGGTGGCCTTTCTGTGATCCTGTCCCTTCCTCAGTGTCTCTTGCCCATTTCTCTCCTTTCCTTTTCTGGGGCTTGGGCCGGTGTTCCTACCTGTCTTTCCCCTCCCCTCCCCACCCCCACACGCCA-G is Pathogenic according to our data. Variant chrX-153797128-GGGCACCCCTGACCCCAGCACCTCCCTTGTAGACTCAGGAAATCACTCAGCCCTTTTGATCATCCCGCCCCTGCTCACAGTCAACAGGGTTCCTATGCGTCCAGTTAGGCCCGGCCATGGGGATCTGGCCTTGTGCCCCCGTAGGGAAGACCAATGCAGAGGGCCAGTCACGGGATTGGTGAGTGTTACTTGGTACCTCCTGCCAGGGACACTGCAGCCCCCAACTGGGCCTAGCCTGCCCACCTGCAGGCCGTGTGAGCAGCGCACAGGGCTCCTCTGCCCACACCCAGAGGGGGCAGAAGGTGACCCTGCCTTTGTTCCCTCACCCAGAACATGGCTCTCTATGCTGACGTCGGTGGAAAACAATTCCCTGTCACTCGAGGCCAGGATGTGGGGCGTTATCAGGTGAGGGGCCAATGGTTCCCTTGCTAGGGGGCTCCCTGCTCCCGGGTGTGACCTGAAGCCCCAGGGGTGGCCGGTCAACCAGGGCCAGGGGCCGTGGGCTCTGGCTGCCGGAGTGCTGCAGTGTCGGCACTGGTGGTCAGGGTGGCCCCTCCGTGTCCACTCTGCCCACACTCTGCTCAACACCCAACCCAGGTGTCCTGGAGCCTGGACCACAAGAGCGCCCACGCAGGCACCTATGAGGTTAGATTCTTCGACGAGGAGTCCTACAGCCTCCTCAGGAAGGTGAGGACTCCTGTAGCCCACTGTGCTCCCCTGTCCCTGGGGAGCAGGATGGGCTGGGTTGGGAGGTGCTGGCAGCAAGTCCTGAGCTGGGTGGCCTTTCTGTGATCCTGTCCCTTCCTCAGTGTCTCTTGCCCATTTCTCTCCTTTCCTTTTCTGGGGCTTGGGCCGGTGTTCCTACCTGTCTTTCCCCTCCCCTCCCCACCCCCACACGCCA-G is described in ClinVar as [Pathogenic]. Clinvar id is 372143.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSR4	NM_006280.3 link	c.187-301_352-15del		exon_loss_variant	Exon 3 of 6	ENST00000370086.8	NP_006271.1	P51571
SSR4	NM_006280.3 link	c.187-301_352-15del		exon_loss_variant	Exon 4 of 6	ENST00000370086.8	NP_006271.1	P51571

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSR4	ENST00000370086.8 link	c.187-329_352-43del		exon_loss_variant	Exon 3 of 6	1	NM_006280.3	ENSP00000359103.3		P51571
SSR4	ENST00000370086.8 link	c.187-329_352-43del		exon_loss_variant	Exon 4 of 6	1	NM_006280.3	ENSP00000359103.3		P51571

Frequencies

GnomAD3 genomes

Cov.:

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

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

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

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.