9-70284951-A-T

Variant names:

• chr9-70284951-A-T
• rs1180122
• NM_015110.4:c.982-1249A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015110.4(SMC5):​c.982-1249A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 151,870 control chromosomes in the GnomAD database, including 3,658 homozygotes. 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: 𝑓 0.22 (3658 hom., cov: 31)
• Consequence: SMC5 NM_015110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.972
• 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMC5	NM_015110.4	c.982-1249A>T		intron_variant	Intron 7 of 24	ENST00000361138.7	NP_055925.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMC5	ENST00000361138.7	c.982-1249A>T		intron_variant	Intron 7 of 24	1	NM_015110.4	ENSP00000354957.5
SMC5	ENST00000618375.1	n.113-1249A>T		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32657 AN: 151752 Hom.: 3648 Cov.: 31

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.215 AC: 32697 AN: 151870 Hom.: 3658 Cov.: 31 AF XY: 0.215 AC XY: 15943 AN XY: 74242

African (AFR) AF: 0.252 AC: 10428 AN: 41378

American (AMR) AF: 0.173 AC: 2641 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3468

East Asian (EAS) AF: 0.263 AC: 1356 AN: 5152

South Asian (SAS) AF: 0.281 AC: 1351 AN: 4804

European-Finnish (FIN) AF: 0.191 AC: 2017 AN: 10548

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13620 AN: 67950

Other (OTH) AF: 0.213 AC: 448 AN: 2106

Alfa AF: 0.111 Hom.: 194

Bravo AF: 0.210

Asia WGS AF: 0.306 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.69
DANN	Benign	0.52
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

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: rs1180122; hg19: chr9-72899867;