NM_015110.4:c.328-594A>C

Variant names:

• chr9-70267329-A-C
• rs1180107
• NM_015110.4:c.328-594A>C

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.328-594A>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SMC5 NM_015110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 1 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]

SMC5 Gene-Disease associations (from GenCC):

• Atelis syndrome 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, G2P

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 (BayesDel_noAF=-0.87).

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.328-594A>C		intron	N/A	NP_055925.2	Q8IY18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMC5	ENST00000361138.7	TSL:1 MANE Select	c.328-594A>C		intron	N/A	ENSP00000354957.5	Q8IY18
	SMC5	ENST00000912980.1		c.328-594A>C		intron	N/A	ENSP00000583039.1
	SMC5	ENST00000884400.1		c.328-594A>C		intron	N/A	ENSP00000554459.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.52
PhyloP100		-0.21

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: rs1180107; hg19: chr9-72882245;