Variant 10-110567687-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4BP6_ModerateBS1BS2

The ENST00000684988.1(SMC3):n.4G>A variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.000437 in 1,101,270 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00048 ( 5 hom. )

Consequence

SMC3
ENST00000684988.1 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.09

Variant links:

Genes affected

SMC3 (HGNC:2468): (structural maintenance of chromosomes 3) This gene belongs to the SMC3 subfamily of SMC proteins. The encoded protein occurs in certain cell types as either an intracellular, nuclear protein or a secreted protein. The nuclear form, known as structural maintenance of chromosomes 3, is a component of the multimeric cohesin complex that holds together sister chromatids during mitosis, enabling proper chromosome segregation. Post-translational modification of the encoded protein by the addition of chondroitin sulfate chains gives rise to the secreted proteoglycan bamacan, an abundant basement membrane protein. [provided by RefSeq, Jul 2008]

SMC3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.16).

BP6

Variant 10-110567687-G-A is Benign according to our data. Variant chr10-110567687-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 368882.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000197 (30/152378) while in subpopulation SAS AF= 0.00559 (27/4834). AF 95% confidence interval is 0.00394. There are 0 homozygotes in gnomad4. There are 20 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 30 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMC3	NM_005445.4 link	c.-130G>A		upstream_gene_variant		ENST00000361804.5	NP_005436.1	Q9UQE7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SMC3	ENST00000684988.1 link	n.4G>A	non_coding_transcript_exon_variant	Exon 1 of 25
SMC3	ENST00000691297.1 link	n.4G>A	non_coding_transcript_exon_variant	Exon 1 of 17
SMC3	ENST00000361804.5 link	c.-130G>A	upstream_gene_variant		1	NM_005445.4	ENSP00000354720.5	Q9UQE7
SMC3	ENST00000691527.1 link	n.-40G>A	upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00558

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000475

AC:

451

AN:

948892

Hom.:

Cov.:

AF XY:

0.000728

AC XY:

355

AN XY:

487840

show subpopulations

Gnomad4 AFR exome

AF:

0.0000869

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00613

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000209

Gnomad4 OTH exome

AF:

0.000164

GnomAD4 genome

AF:

0.000197

AC:

AN:

152378

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000604

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

De Lange syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.98

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.

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