Variant 10-110577944-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005445.4(SMC3):c.350+30T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 1,441,184 control chromosomes in the GnomAD database, including 4,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 1869 hom., cov: 32)

Exomes 𝑓: 0.053 ( 2918 hom. )

Consequence

SMC3
NM_005445.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.952

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 10-110577944-T-G is Benign according to our data. Variant chr10-110577944-T-G is described in ClinVar as [Benign]. Clinvar id is 1285681.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC3	NM_005445.4 linkuse as main transcript	c.350+30T>G		intron_variant		ENST00000361804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC3	ENST00000361804.5 linkuse as main transcript	c.350+30T>G		intron_variant		1	NM_005445.4	P1

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16928

AN:

151948

Hom.:

1858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.0330

Gnomad AMR

AF:

0.0632

Gnomad ASJ

AF:

0.0446

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0435

Gnomad FIN

AF:

0.0507

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0447

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.0578

AC:

14358

AN:

248366

Hom.:

907

AF XY:

0.0544

AC XY:

7321

AN XY:

134526

show subpopulations

Gnomad AFR exome

AF:

0.287

Gnomad AMR exome

AF:

0.0408

Gnomad ASJ exome

AF:

0.0425

Gnomad EAS exome

AF:

0.000439

Gnomad SAS exome

AF:

0.0425

Gnomad FIN exome

AF:

0.0484

Gnomad NFE exome

AF:

0.0469

Gnomad OTH exome

AF:

0.0590

GnomAD4 exome

AF:

0.0525

AC:

67708

AN:

1289118

Hom.:

2918

Cov.:

AF XY:

0.0516

AC XY:

33574

AN XY:

650592

show subpopulations

Gnomad4 AFR exome

AF:

0.298

Gnomad4 AMR exome

AF:

0.0440

Gnomad4 ASJ exome

AF:

0.0416

Gnomad4 EAS exome

AF:

0.000155

Gnomad4 SAS exome

AF:

0.0450

Gnomad4 FIN exome

AF:

0.0485

Gnomad4 NFE exome

AF:

0.0475

Gnomad4 OTH exome

AF:

0.0641

GnomAD4 genome

AF:

0.112

AC:

16983

AN:

152066

Hom.:

1869

Cov.:

AF XY:

0.109

AC XY:

8096

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.285

Gnomad4 AMR

AF:

0.0630

Gnomad4 ASJ

AF:

0.0446

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0437

Gnomad4 FIN

AF:

0.0507

Gnomad4 NFE

AF:

0.0447

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.0328

Hom.:

Bravo

AF:

0.121

Asia WGS

AF:

0.0440

AC:

154

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.6

DANN

Benign

0.32

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