chr8-125151154-A-AT

Position:

• chr8-125151154-A-AT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_173685.4(NSMCE2):​c.158-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,381,122 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (0 hom.)
• Consequence: NSMCE2 NM_173685.4 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.234

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]

NSMCE2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 8-125151154-A-AT is Benign according to our data. Variant chr8-125151154-A-AT is described in ClinVar as [Benign]. Clinvar id is 1598963.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSMCE2	NM_173685.4	c.158-8dupT		splice_region_variant, intron_variant		ENST00000287437.8	NP_775956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSMCE2	ENST00000287437.8	c.158-8dupT		splice_region_variant, intron_variant		1	NM_173685.4	ENSP00000287437.3

Frequencies

GnomAD3 genomes AF: 0.000139 AC: 21 AN: 151296 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000962

GnomAD4 exome AF: 0.00148 AC: 1816 AN: 1229708 Hom.: 0 Cov.: 17 AF XY: 0.00145 AC XY: 899 AN XY: 618876

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.000880

Gnomad4 ASJ exome AF: 0.000756

Gnomad4 EAS exome AF: 0.000614

Gnomad4 SAS exome AF: 0.00220

Gnomad4 FIN exome AF: 0.000534

Gnomad4 NFE exome AF: 0.00158

Gnomad4 OTH exome AF: 0.00125

GnomAD4 genome AF: 0.000139 AC: 21 AN: 151414 Hom.: 0 Cov.: 31 AF XY: 0.000149 AC XY: 11 AN XY: 73974

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.000952

Bravo AF: 0.000113

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 21, 2024

- -

Computational scores

Source: dbNSFP v4.3

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: rs553942139; hg19: chr8-126163396;