rs7004739

Positions:

• chr8-125316141-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173685.4(NSMCE2):​c.419-41078G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 152,036 control chromosomes in the GnomAD database, including 17,609 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 0.45 (17609 hom., cov: 32)
• Consequence: NSMCE2 NM_173685.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297

Genes affected

NSMCE2 (HGNC:26513): (NSE2 (MMS21) homolog, SMC5-SMC6 complex SUMO ligase) This gene encodes a member of a family of E3 small ubiquitin-related modifier (SUMO) ligases that mediates the attachment of a SUMO protein to proteins involved in nuclear transport, transcription, chromosome segregation and DNA repair. The encoded protein is part of the structural maintenance of chromosomes (SMC) 5/6 complex which plays a key role genome maintenance, facilitating chromosome segregation and suppressing mitotic recombination. A knockout of the orthologous mouse gene is lethal prior to embryonic day 10.5. Naturally occurring mutations in this gene, that abolish the SUMO ligase activity, are associated with primordial dwarfism and extreme insulin resistance. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSMCE2	NM_173685.4	c.419-41078G>A		intron_variant		ENST00000287437.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSMCE2	ENST00000287437.8	c.419-41078G>A		intron_variant		1	NM_173685.4	P1
NSMCE2	ENST00000517315.1	c.239-41078G>A		intron_variant		3
NSMCE2	ENST00000517532.5	c.419-41078G>A		intron_variant		5
NSMCE2	ENST00000522563.5	c.419-41078G>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68029 AN: 151918 Hom.: 17609 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.447 AC: 68030 AN: 152036 Hom.: 17609 Cov.: 32 AF XY: 0.450 AC XY: 33415 AN XY: 74306

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.488

Alfa AF: 0.499 Hom.: 5467

Bravo AF: 0.443

Asia WGS AF: 0.427 AC: 1487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs7004739; hg19: chr8-126328383;