rs7075340

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_005445.4(SMC3):c.2116+23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,611,826 control chromosomes in the GnomAD database, including 784,671 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 71443 hom., cov: 32)

Exomes 𝑓: 0.99 ( 713228 hom. )

Consequence

SMC3
NM_005445.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.00

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 10-110596573-G-A is Benign according to our data. Variant chr10-110596573-G-A is described in ClinVar as [Benign]. Clinvar id is 259768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMC3	NM_005445.4 link	c.2116+23G>A		intron_variant	Intron 19 of 28	ENST00000361804.5	NP_005436.1	Q9UQE7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SMC3	ENST00000361804.5 link	c.2116+23G>A	intron_variant	Intron 19 of 28	1	NM_005445.4	ENSP00000354720.5	Q9UQE7
SMC3	ENST00000684988.1 link	n.2784G>A	non_coding_transcript_exon_variant	Exon 17 of 25
SMC3	ENST00000692792.1 link	n.2258G>A	non_coding_transcript_exon_variant	Exon 19 of 19

Frequencies

GnomAD3 genomes

AF:

0.968

AC:

147355

AN:

152188

Hom.:

71391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.924

Gnomad AMI

AF:

0.968

Gnomad AMR

AF:

0.949

Gnomad ASJ

AF:

0.989

Gnomad EAS

AF:

0.967

Gnomad SAS

AF:

0.995

Gnomad FIN

AF:

0.989

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.993

Gnomad OTH

AF:

0.965

GnomAD3 exomes

AF:

0.978

AC:

244304

AN:

249886

Hom.:

119530

AF XY:

0.982

AC XY:

133010

AN XY:

135434

show subpopulations

Gnomad AFR exome

AF:

0.923

Gnomad AMR exome

AF:

0.927

Gnomad ASJ exome

AF:

0.988

Gnomad EAS exome

AF:

0.968

Gnomad SAS exome

AF:

0.997

Gnomad FIN exome

AF:

0.989

Gnomad NFE exome

AF:

0.994

Gnomad OTH exome

AF:

0.981

GnomAD4 exome

AF:

0.988

AC:

1442670

AN:

1459520

Hom.:

713228

Cov.:

AF XY:

0.989

AC XY:

718430

AN XY:

726174

show subpopulations

Gnomad4 AFR exome

AF:

0.923

Gnomad4 AMR exome

AF:

0.928

Gnomad4 ASJ exome

AF:

0.988

Gnomad4 EAS exome

AF:

0.957

Gnomad4 SAS exome

AF:

0.997

Gnomad4 FIN exome

AF:

0.989

Gnomad4 NFE exome

AF:

0.994

Gnomad4 OTH exome

AF:

0.983

GnomAD4 genome

AF:

0.968

AC:

147465

AN:

152306

Hom.:

71443

Cov.:

AF XY:

0.968

AC XY:

72129

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.924

Gnomad4 AMR

AF:

0.949

Gnomad4 ASJ

AF:

0.989

Gnomad4 EAS

AF:

0.967

Gnomad4 SAS

AF:

0.995

Gnomad4 FIN

AF:

0.989

Gnomad4 NFE

AF:

0.993

Gnomad4 OTH

AF:

0.966

Alfa

AF:

0.986

Hom.:

71469

Bravo

AF:

0.962

Asia WGS

AF:

0.973

AC:

3385

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cornelia de Lange syndrome 3

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: 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

-0.94

CADD

Benign

0.28

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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