NM_015110.4:c.58C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015110.4(SMC5):​c.58C>T​(p.Leu20Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L20V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

SMC5
NM_015110.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.411
Variant links:
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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.061313123).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SMC5NM_015110.4 linkc.58C>T p.Leu20Phe missense_variant Exon 1 of 25 ENST00000361138.7 NP_055925.2 Q8IY18

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMC5ENST00000361138.7 linkc.58C>T p.Leu20Phe missense_variant Exon 1 of 25 1 NM_015110.4 ENSP00000354957.5 Q8IY18

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152264
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152264
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.064
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
12
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0072
T
Eigen
Benign
-0.84
Eigen_PC
Benign
-0.81
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.59
T
M_CAP
Benign
0.0086
T
MetaRNN
Benign
0.061
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.51
N
REVEL
Benign
0.034
Sift
Benign
0.069
T
Sift4G
Benign
0.25
T
Polyphen
0.23
B
Vest4
0.11
MutPred
0.19
Loss of stability (P = 0.151);
MVP
0.082
MPC
0.16
ClinPred
0.11
T
GERP RS
2.7
Varity_R
0.085
gMVP
0.18

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: rs1342654623; hg19: chr9-72874052; API