chr10-110569080-C-G

Variant summary

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

The NM_005445.4(SMC3):​c.91+67C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,041,970 control chromosomes in the GnomAD database, including 520,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 75870 hom., cov: 32)
Exomes 𝑓: 1.0 ( 444618 hom. )

Consequence

SMC3
NM_005445.4 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.02
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]

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=-0.92).
BP6
Variant 10-110569080-C-G is Benign according to our data. Variant chr10-110569080-C-G is described in ClinVar as [Benign]. Clinvar id is 674950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SMC3NM_005445.4 linkuse as main transcriptc.91+67C>G intron_variant ENST00000361804.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SMC3ENST00000361804.5 linkuse as main transcriptc.91+67C>G intron_variant 1 NM_005445.4 P1

Frequencies

GnomAD3 genomes
AF:
0.998
AC:
151935
AN:
152250
Hom.:
75810
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.993
Gnomad AMI
AF:
1.00
Gnomad AMR
AF:
0.999
Gnomad ASJ
AF:
1.00
Gnomad EAS
AF:
1.00
Gnomad SAS
AF:
1.00
Gnomad FIN
AF:
1.00
Gnomad MID
AF:
1.00
Gnomad NFE
AF:
1.00
Gnomad OTH
AF:
0.998
GnomAD4 exome
AF:
1.00
AC:
889418
AN:
889602
Hom.:
444618
AF XY:
1.00
AC XY:
466152
AN XY:
466232
show subpopulations
Gnomad4 AFR exome
AF:
0.993
Gnomad4 AMR exome
AF:
1.00
Gnomad4 ASJ exome
AF:
1.00
Gnomad4 EAS exome
AF:
1.00
Gnomad4 SAS exome
AF:
1.00
Gnomad4 FIN exome
AF:
1.00
Gnomad4 NFE exome
AF:
1.00
Gnomad4 OTH exome
AF:
1.00
GnomAD4 genome
AF:
0.998
AC:
152054
AN:
152368
Hom.:
75870
Cov.:
32
AF XY:
0.998
AC XY:
74375
AN XY:
74514
show subpopulations
Gnomad4 AFR
AF:
0.993
Gnomad4 AMR
AF:
0.999
Gnomad4 ASJ
AF:
1.00
Gnomad4 EAS
AF:
1.00
Gnomad4 SAS
AF:
1.00
Gnomad4 FIN
AF:
1.00
Gnomad4 NFE
AF:
1.00
Gnomad4 OTH
AF:
0.998
Alfa
AF:
1.00
Hom.:
3365
Bravo
AF:
0.998
Asia WGS
AF:
1.00
AC:
3467
AN:
3468

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 submitterclinical testingGeneDxJun 16, 2018This 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
2.2
DANN
Benign
0.56

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.

Other links and lift over

dbSNP: rs4917577; hg19: chr10-112328838; API