Variant X-153796262-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006280.3(SSR4):c.68-172T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 432,172 control chromosomes in the GnomAD database, including 38 homozygotes. There are 2,048 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.014 ( 14 hom., 461 hem., cov: 25)

Exomes 𝑓: 0.016 ( 24 hom. 1587 hem. )

Consequence

SSR4
NM_006280.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.567

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant X-153796262-T-C is Benign according to our data. Variant chrX-153796262-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1706820.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-153796262-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0138 (1555/112794) while in subpopulation NFE AF= 0.02 (1065/53291). AF 95% confidence interval is 0.019. There are 14 homozygotes in gnomad4. There are 461 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSR4	NM_006280.3 linkuse as main transcript	c.68-172T>C		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.68-172T>C		intron_variant		1	NM_006280.3	ENSP00000359103	P1

Frequencies

GnomAD3 genomes

AF:

0.0138

AC:

1555

AN:

112740

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

461

AN XY:

34886

show subpopulations

Gnomad AFR

AF:

0.00283

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.00654

Gnomad ASJ

AF:

0.0162

Gnomad EAS

AF:

0.000554

Gnomad SAS

AF:

0.00254

Gnomad FIN

AF:

0.0199

Gnomad MID

AF:

0.00840

Gnomad NFE

AF:

0.0200

Gnomad OTH

AF:

0.0105

GnomAD4 exome

AF:

0.0159

AC:

5072

AN:

319378

Hom.:

Cov.:

AF XY:

0.0153

AC XY:

1587

AN XY:

104028

show subpopulations

Gnomad4 AFR exome

AF:

0.00290

Gnomad4 AMR exome

AF:

0.00581

Gnomad4 ASJ exome

AF:

0.0146

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00548

Gnomad4 FIN exome

AF:

0.0261

Gnomad4 NFE exome

AF:

0.0193

Gnomad4 OTH exome

AF:

0.0166

GnomAD4 genome

AF:

0.0138

AC:

1555

AN:

112794

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

461

AN XY:

34950

show subpopulations

Gnomad4 AFR

AF:

0.00283

Gnomad4 AMR

AF:

0.00653

Gnomad4 ASJ

AF:

0.0162

Gnomad4 EAS

AF:

0.000555

Gnomad4 SAS

AF:

0.00255

Gnomad4 FIN

AF:

0.0199

Gnomad4 NFE

AF:

0.0200

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0160

Hom.:

Bravo

AF:

0.0135

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 29, 2020

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.3

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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