Variant 9-70264388-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015110.4(SMC5):c.270G>A(p.Val90=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00344 in 1,614,042 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 83 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 84 hom. )

Consequence

SMC5
NM_015110.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0400

Variant links:

Genes affected

SMC5 (HGNC:20465): (structural maintenance of chromosomes 5) Predicted to enable ATP binding activity. Involved in several processes, including DNA recombination; cellular senescence; and positive regulation of maintenance of mitotic sister chromatid cohesion. Located in cell junction; chromosome; and nuclear body. Part of Smc5-Smc6 complex. [provided by Alliance of Genome Resources, Apr 2022]

SMC5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 9-70264388-G-A is Benign according to our data. Variant chr9-70264388-G-A is described in ClinVar as [Benign]. Clinvar id is 791299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC5	NM_015110.4 linkuse as main transcript	c.270G>A	p.Val90=	synonymous_variant	2/25	ENST00000361138.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC5	ENST00000361138.7 linkuse as main transcript	c.270G>A	p.Val90=	synonymous_variant	2/25	1	NM_015110.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0183

AC:

2778

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0639

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00478

AC:

1202

AN:

251436

Hom.:

AF XY:

0.00342

AC XY:

465

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.0637

Gnomad AMR exome

AF:

0.00382

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00190

AC:

2772

AN:

1461734

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

1194

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.0659

Gnomad4 AMR exome

AF:

0.00380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000989

Gnomad4 OTH exome

AF:

0.00436

GnomAD4 genome

AF:

0.0183

AC:

2780

AN:

152308

Hom.:

Cov.:

AF XY:

0.0174

AC XY:

1293

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0637

Gnomad4 AMR

AF:

0.00627

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00953

Hom.:

Bravo

AF:

0.0208

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

4.0

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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