9-70259152-C-T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_015110.4(SMC5):c.74C>T(p.Ser25Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SMC5
NM_015110.4 missense
NM_015110.4 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 0.781
Publications
0 publications found
Genes affected
SMC5 (HGNC:20465): (structural maintenance of chromosomes 5) Predicted to enable ATP binding activity. Involved in several processes, including DNA recombination; cellular senescence; and positive regulation of maintenance of mitotic sister chromatid cohesion. Located in cell junction; chromosome; and nuclear body. Part of Smc5-Smc6 complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM1
In a modified_residue Phosphoserine (size 0) in uniprot entity SMC5_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08906731).
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_015110.4. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SMC5 | TSL:1 MANE Select | c.74C>T | p.Ser25Leu | missense | Exon 1 of 25 | ENSP00000354957.5 | Q8IY18 | ||
| SMC5 | c.74C>T | p.Ser25Leu | missense | Exon 1 of 26 | ENSP00000583039.1 | ||||
| SMC5 | c.74C>T | p.Ser25Leu | missense | Exon 1 of 24 | ENSP00000554459.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152254Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152254
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460118Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726186 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1460118
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
726186
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33442
American (AMR)
AF:
AC:
0
AN:
44504
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26084
East Asian (EAS)
AF:
AC:
0
AN:
39652
South Asian (SAS)
AF:
AC:
0
AN:
85830
European-Finnish (FIN)
AF:
AC:
0
AN:
53228
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111294
Other (OTH)
AF:
AC:
0
AN:
60318
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152254Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74382 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152254
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74382
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41474
American (AMR)
AF:
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3466
East Asian (EAS)
AF:
AC:
0
AN:
5200
South Asian (SAS)
AF:
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
AC:
0
AN:
10628
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68044
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.725
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
0
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Inborn genetic diseases (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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