chr9-70259107-C-A

Variant names:

• chr9-70259107-C-A
• rs1475684118
• NM_015110.4:c.29C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015110.4(SMC5):​c.29C>A​(p.Thr10Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. T10I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SMC5 NM_015110.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.766
• 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]

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

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

ACMG classification

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=0.060709238).

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>A	p.Thr10Asn	missense	Exon 1 of 25	NP_055925.2	Q8IY18
	SMC5-DT	NR_039990.1		n.-233G>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMC5	ENST00000361138.7	TSL:1 MANE Select	c.29C>A	p.Thr10Asn	missense	Exon 1 of 25	ENSP00000354957.5	Q8IY18
	SMC5	ENST00000912980.1		c.29C>A	p.Thr10Asn	missense	Exon 1 of 26	ENSP00000583039.1
	SMC5	ENST00000884400.1		c.29C>A	p.Thr10Asn	missense	Exon 1 of 24	ENSP00000554459.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.3
DANN	Benign	0.91
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.77
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.012
Sift	Benign	0.13	T
Sift4G	Benign	0.078	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.23		Loss of phosphorylation at T10 (P = 7e-04)
MVP		0.21
MPC		0.17
ClinPred		0.059	T
GERP RS		0.64
PromoterAI		-0.0024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.085
gMVP		0.16
Mutation Taster		=96/4	polymorphism

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: rs1475684118; hg19: chr9-72874023;