X-53422841-A-G

Variant names:

• chrX-53422841-A-G
• rs148778658
• ENST00000329209:c.-169A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000329209(RIBC1):​c.-169A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00325 in 346,181 control chromosomes in the GnomAD database, including 13 homozygotes. There are 310 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 0.0079 (11 hom., 256 hem., cov: 24)
  • Exomes 𝑓: 0.00099 (2 hom. 54 hem.)
• Consequence: RIBC1 ENST00000329209 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.62

Genes affected

RIBC1 (HGNC:26537): (RIB43A domain with coiled-coils 1)

SMC1A (HGNC:11111): (structural maintenance of chromosomes 1A) Proper cohesion of sister chromatids is a prerequisite for the correct segregation of chromosomes during cell division. The cohesin multiprotein complex is required for sister chromatid cohesion. This complex is composed partly of two structural maintenance of chromosomes (SMC) proteins, SMC3 and either SMC1B or the protein encoded by this gene. Most of the cohesin complexes dissociate from the chromosomes before mitosis, although those complexes at the kinetochore remain. Therefore, the encoded protein is thought to be an important part of functional kinetochores. In addition, this protein interacts with BRCA1 and is phosphorylated by ATM, indicating a potential role for this protein in DNA repair. This gene, which belongs to the SMC gene family, is located in an area of the X-chromosome that escapes X inactivation. Mutations in this gene result in Cornelia de Lange syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-53422841-A-G is Benign according to our data. Variant chrX-53422841-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1209126.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00794 (895/112787) while in subpopulation AFR AF= 0.0273 (849/31109). AF 95% confidence interval is 0.0258. There are 11 homozygotes in gnomad4. There are 256 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMC1A	NM_006306.4	c.-241T>C		upstream_gene_variant		ENST00000322213.9	NP_006297.2
RIBC1	NM_001031745.5	c.-253A>G		upstream_gene_variant		ENST00000375327.6	NP_001026915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMC1A	ENST00000322213.9	c.-241T>C		upstream_gene_variant		1	NM_006306.4	ENSP00000323421.3
RIBC1	ENST00000375327.6	c.-253A>G		upstream_gene_variant		1	NM_001031745.5	ENSP00000364476.3

Frequencies

GnomAD3 genomes AF: 0.00796 AC: 897 AN: 112736 Hom.: 11 Cov.: 24 AF XY: 0.00736 AC XY: 257 AN XY: 34898

Gnomad AFR AF: 0.0274

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000939

Gnomad OTH AF: 0.00986

GnomAD4 exome AF: 0.000990 AC: 231 AN: 233394 Hom.: 2 Cov.: 0 AF XY: 0.000756 AC XY: 54 AN XY: 71436

Gnomad4 AFR exome AF: 0.0263

Gnomad4 AMR exome AF: 0.000880

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000366

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000724

Gnomad4 OTH exome AF: 0.00208

GnomAD4 genome AF: 0.00794 AC: 895 AN: 112787 Hom.: 11 Cov.: 24 AF XY: 0.00732 AC XY: 256 AN XY: 34959

Gnomad4 AFR AF: 0.0273

Gnomad4 AMR AF: 0.00241

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000939

Gnomad4 OTH AF: 0.00975

Alfa AF: 0.00577 Hom.: 12

Bravo AF: 0.00923

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 25, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.0090
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs148778658; hg19: chrX-53449790;