rs7075340

Variant names:

• chr10-110596573-G-A
• rs7075340
• NM_005445.4:c.2116+23G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-110596573-G-A
• chr10-110596573-G-C
• chr10-110596573-G-T

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: -1.00
• Publications: 6 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 -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 VariationId 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.

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.2116+23G>A		intron	N/A	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.2116+23G>A		intron	N/A	ENSP00000354720.5	Q9UQE7
	SMC3	ENST00000918257.1		c.2140+23G>A		intron	N/A	ENSP00000588316.1
	SMC3	ENST00000966376.1		c.2134+23G>A		intron	N/A	ENSP00000636435.1

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

GnomAD2 exomes AF: 0.978 AC: 244304 AN: 249886 AF XY: 0.982

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 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

African (AFR) AF: 0.923 AC: 30836 AN: 33396

American (AMR) AF: 0.928 AC: 41467 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 25785 AN: 26096

East Asian (EAS) AF: 0.957 AC: 37931 AN: 39632

South Asian (SAS) AF: 0.997 AC: 85837 AN: 86120

European-Finnish (FIN) AF: 0.989 AC: 52641 AN: 53202

Middle Eastern (MID) AF: 0.991 AC: 5706 AN: 5760

European-Non Finnish (NFE) AF: 0.994 AC: 1103179 AN: 1110360

Other (OTH) AF: 0.983 AC: 59288 AN: 60290

GnomAD4 genome AF: 0.968 AC: 147465 AN: 152306 Hom.: 71443 Cov.: 32 AF XY: 0.968 AC XY: 72129 AN XY: 74502

African (AFR) AF: 0.924 AC: 38403 AN: 41540

American (AMR) AF: 0.949 AC: 14521 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 3431 AN: 3468

East Asian (EAS) AF: 0.967 AC: 5009 AN: 5180

South Asian (SAS) AF: 0.995 AC: 4803 AN: 4828

European-Finnish (FIN) AF: 0.989 AC: 10502 AN: 10620

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.993 AC: 67581 AN: 68044

Other (OTH) AF: 0.966 AC: 2043 AN: 2116

Alfa AF: 0.982 Hom.: 93009

Bravo AF: 0.962

Asia WGS AF: 0.973 AC: 3385 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.28
DANN	Benign	0.61
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7075340; hg19: chr10-112356331;