rs7075340

chr10-110596573-G-Achr10-110596573-G-Cchr10-110596573-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.00

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]

ACMG classification

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/exons	MANE	UniProt
SMC3	NM_005445.4	c.2116+23G>A		intron_variant		ENST00000361804.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC3	ENST00000361804.5	c.2116+23G>A		intron_variant		1	NM_005445.4	P1
SMC3	ENST00000684988.1	n.2784G>A		non_coding_transcript_exon_variant	17/25
SMC3	ENST00000692792.1	n.2258G>A		non_coding_transcript_exon_variant	19/19

Frequencies

GnomAD3 genomes AF: 0.968 AC: 147355 AN: 152188 Hom.: 71391 Cov.: 32

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

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.: 29 AF XY: 0.989 AC XY: 718430 AN XY: 726174

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.: 32 AF XY: 0.968 AC XY: 72129 AN XY: 74502

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

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. -

Cornelia de Lange syndrome 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

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

Other links and lift over

dbSNP: rs7075340; hg19: chr10-112356331;