chr10-110567743-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005445.4(SMC3):​c.-74C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,577,144 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0013 ( 3 hom. )

Consequence

SMC3
NM_005445.4 5_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.765
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 -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
Variant 10-110567743-C-A is Benign according to our data. Variant chr10-110567743-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 298761.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00123 (188/152348) while in subpopulation AMR AF= 0.00333 (51/15310). AF 95% confidence interval is 0.0026. There are 0 homozygotes in gnomad4. There are 107 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High AC in GnomAd4 at 188 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SMC3NM_005445.4 linkuse as main transcriptc.-74C>A 5_prime_UTR_variant 1/29 ENST00000361804.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SMC3ENST00000361804.5 linkuse as main transcriptc.-74C>A 5_prime_UTR_variant 1/291 NM_005445.4 P1
SMC3ENST00000684988.1 linkuse as main transcriptn.60C>A non_coding_transcript_exon_variant 1/25
SMC3ENST00000691297.1 linkuse as main transcriptn.60C>A non_coding_transcript_exon_variant 1/17
SMC3ENST00000691527.1 linkuse as main transcriptn.17C>A non_coding_transcript_exon_variant 1/16

Frequencies

GnomAD3 genomes
AF:
0.00123
AC:
188
AN:
152230
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00334
Gnomad ASJ
AF:
0.00173
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000827
Gnomad FIN
AF:
0.00122
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00143
Gnomad OTH
AF:
0.00287
GnomAD4 exome
AF:
0.00132
AC:
1885
AN:
1424796
Hom.:
3
Cov.:
26
AF XY:
0.00135
AC XY:
960
AN XY:
710646
show subpopulations
Gnomad4 AFR exome
AF:
0.000153
Gnomad4 AMR exome
AF:
0.00144
Gnomad4 ASJ exome
AF:
0.00128
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.000984
Gnomad4 FIN exome
AF:
0.000781
Gnomad4 NFE exome
AF:
0.00144
Gnomad4 OTH exome
AF:
0.00162
GnomAD4 genome
AF:
0.00123
AC:
188
AN:
152348
Hom.:
0
Cov.:
34
AF XY:
0.00144
AC XY:
107
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.000240
Gnomad4 AMR
AF:
0.00333
Gnomad4 ASJ
AF:
0.00173
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000827
Gnomad4 FIN
AF:
0.00122
Gnomad4 NFE
AF:
0.00143
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.000265
Hom.:
0
Bravo
AF:
0.00150
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Cornelia de Lange syndrome 3 Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
CADD
Benign
10
DANN
Benign
0.85
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.1

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs376252081; hg19: chr10-112327501; API