rs2419565

Variant names:

• chr10-110602112-A-G
• rs2419565
• NM_005445.4:c.3039A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-110602112-A-G
• chr10-110602112-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005445.4(SMC3):​c.3039A>G​(p.Ser1013Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.989 in 152,322 control chromosomes in the GnomAD database, including 74,577 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (74577 hom., cov: 32)
  • Exomes 𝑓: 1.0 (728596 hom.)
  • Failed GnomAD Quality Control
• Consequence: SMC3 NM_005445.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.0810
• Publications: 25 publications found

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 Gene-Disease associations (from GenCC):

• Cornelia de Lange syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Cornelia de Lange syndrome 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 10-110602112-A-G is Benign according to our data. Variant chr10-110602112-A-G is described in ClinVar as Benign. ClinVar VariationId is 159985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.081 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005445.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMC3	NM_005445.4	MANE Select	c.3039A>G	p.Ser1013Ser	synonymous	Exon 25 of 29	NP_005436.1	Q9UQE7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMC3	ENST00000361804.5	TSL:1 MANE Select	c.3039A>G	p.Ser1013Ser	synonymous	Exon 25 of 29	ENSP00000354720.5	Q9UQE7
	SMC3	ENST00000918257.1		c.3063A>G	p.Ser1021Ser	synonymous	Exon 25 of 29	ENSP00000588316.1
	SMC3	ENST00000966376.1		c.3057A>G	p.Ser1019Ser	synonymous	Exon 25 of 29	ENSP00000636435.1

Frequencies

GnomAD3 genomes AF: 0.989 AC: 150603 AN: 152204 Hom.: 74519 Cov.: 32

Gnomad AFR AF: 0.965

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.996

Gnomad ASJ AF: 0.990

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.992

GnomAD2 exomes AF: 0.997 AC: 250329 AN: 251144 AF XY: 0.997

Gnomad AFR exome AF: 0.965

Gnomad AMR exome AF: 0.998

Gnomad ASJ exome AF: 0.989

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.998

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.999 AC: 1459326 AN: 1461506 Hom.: 728596 Cov.: 45 AF XY: 0.999 AC XY: 726033 AN XY: 727058

African (AFR) AF: 0.964 AC: 32264 AN: 33464

American (AMR) AF: 0.998 AC: 44620 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 25843 AN: 26126

East Asian (EAS) AF: 1.00 AC: 39618 AN: 39618

South Asian (SAS) AF: 1.00 AC: 86211 AN: 86230

European-Finnish (FIN) AF: 1.00 AC: 53416 AN: 53416

Middle Eastern (MID) AF: 0.996 AC: 5741 AN: 5764

European-Non Finnish (NFE) AF: 1.00 AC: 1111438 AN: 1111790

Other (OTH) AF: 0.997 AC: 60175 AN: 60378

GnomAD4 genome AF: 0.989 AC: 150720 AN: 152322 Hom.: 74577 Cov.: 32 AF XY: 0.990 AC XY: 73734 AN XY: 74488

African (AFR) AF: 0.965 AC: 40104 AN: 41562

American (AMR) AF: 0.996 AC: 15238 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.990 AC: 3438 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5186

South Asian (SAS) AF: 0.999 AC: 4831 AN: 4834

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10618

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68006 AN: 68032

Other (OTH) AF: 0.992 AC: 2095 AN: 2112

Alfa AF: 0.993 Hom.: 55277

Bravo AF: 0.988

Asia WGS AF: 0.997 AC: 3467 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 1.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	Cornelia de Lange syndrome 3 (3)
-	-	2	not provided (2)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.89
DANN	Benign	0.46
PhyloP100		0.081
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2419565; hg19: chr10-112361870; COSMIC: COSV62418881;