Genetic Variant NM_015110.4:c.29C>T (chr9-70259107-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015110.4(SMC5):c.29C>T(p.Thr10Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SMC5
NM_015110.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.766

Publications

0 publications found

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]

SMC5 links:

MAMDC2-AS1 (HGNC:48719): (MAMDC2 antisense RNA 1)

MAMDC2-AS1 links:

SMC5-DT (HGNC:48718): (SMC5 divergent transcript)

SMC5-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06634629).

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.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMC5	NM_015110.4	MANE Select	c.29C>T	p.Thr10Ile	missense	Exon 1 of 25	NP_055925.2	Q8IY18
	SMC5-DT	NR_039990.1		n.-233G>A		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMC5	ENST00000361138.7	TSL:1 MANE Select	c.29C>T	p.Thr10Ile	missense	Exon 1 of 25	ENSP00000354957.5	Q8IY18
SMC5	ENST00000912980.1		c.29C>T	p.Thr10Ile	missense	Exon 1 of 26	ENSP00000583039.1
SMC5	ENST00000884400.1		c.29C>T	p.Thr10Ile	missense	Exon 1 of 24	ENSP00000554459.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000406

AC:

AN:

246440

AF XY:

0.00000749

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459110

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725700

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33384

American (AMR)

AF:

0.00

AC:

AN:

44340

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39502

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110724

Other (OTH)

AF:

0.0000166

AC:

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0042

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.68

M_CAP

Benign

0.010

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.77

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.44

REVEL

Benign

0.0090

Sift

Benign

0.062

Sift4G

Uncertain

0.037

Polyphen

0.037

Vest4

0.18

MutPred

0.25

Loss of phosphorylation at T10 (P = 7e-04)

MVP

0.15

MPC

0.16

ClinPred

0.053

GERP RS

0.64

PromoterAI

0.017

Neutral

(source)

Varity_R

0.074

gMVP

0.23

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over