Variant X-153796320-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006280.3(SSR4):c.68-114A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 514,588 control chromosomes in the GnomAD database, including 35,665 homozygotes. There are 75,295 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 7826 hom., 14909 hem., cov: 24)

Exomes 𝑓: 0.43 ( 27839 hom. 60386 hem. )

Consequence

SSR4
NM_006280.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.53

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant X-153796320-A-G is Benign according to our data. Variant chrX-153796320-A-G is described in ClinVar as [Benign]. Clinvar id is 1255220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153796320-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSR4	NM_006280.3 linkuse as main transcript	c.68-114A>G		intron_variant		ENST00000370086.8	NP_006271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSR4	ENST00000370086.8 linkuse as main transcript	c.68-114A>G		intron_variant		1	NM_006280.3	ENSP00000359103	P1

Frequencies

GnomAD3 genomes

AF:

0.431

AC:

48062

AN:

111406

Hom.:

7820

Cov.:

AF XY:

0.442

AC XY:

14868

AN XY:

33612

show subpopulations

Gnomad AFR

AF:

0.500

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.558

Gnomad ASJ

AF:

0.457

Gnomad EAS

AF:

0.833

Gnomad SAS

AF:

0.709

Gnomad FIN

AF:

0.386

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.330

Gnomad OTH

AF:

0.468

GnomAD4 exome

AF:

0.435

AC:

175268

AN:

403130

Hom.:

27839

Cov.:

AF XY:

0.458

AC XY:

60386

AN XY:

131928

show subpopulations

Gnomad4 AFR exome

AF:

0.513

Gnomad4 AMR exome

AF:

0.648

Gnomad4 ASJ exome

AF:

0.489

Gnomad4 EAS exome

AF:

0.808

Gnomad4 SAS exome

AF:

0.705

Gnomad4 FIN exome

AF:

0.380

Gnomad4 NFE exome

AF:

0.336

Gnomad4 OTH exome

AF:

0.437

GnomAD4 genome

AF:

0.432

AC:

48108

AN:

111458

Hom.:

7826

Cov.:

AF XY:

0.443

AC XY:

14909

AN XY:

33674

show subpopulations

Gnomad4 AFR

AF:

0.501

Gnomad4 AMR

AF:

0.558

Gnomad4 ASJ

AF:

0.457

Gnomad4 EAS

AF:

0.833

Gnomad4 SAS

AF:

0.707

Gnomad4 FIN

AF:

0.386

Gnomad4 NFE

AF:

0.330

Gnomad4 OTH

AF:

0.473

Alfa

AF:

0.390

Hom.:

9916

Bravo

AF:

0.452

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

7.4

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over