rs886037827
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_138704.4(NSMCE3):c.626C>T(p.Pro209Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,116 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
NSMCE3
NM_138704.4 missense
NM_138704.4 missense
Scores
2
7
9
Clinical Significance
Conservation
PhyloP100: 3.09
Genes affected
NSMCE3 (HGNC:7677): (NSE3 homolog, SMC5-SMC6 complex component) The protein encoded by this gene is part of the SMC5-6 chromatin reorganizing complex and is a member of the MAGE superfamily. This is an intronless gene. [provided by RefSeq, May 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 15-29269080-G-A is Pathogenic according to our data. Variant chr15-29269080-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 267796.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-29269080-G-A is described in UniProt as null. Variant chr15-29269080-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NSMCE3 | NM_138704.4 | c.626C>T | p.Pro209Leu | missense_variant | 1/1 | ENST00000332303.6 | |
ENTREP2 | NM_015307.2 | c.277-16602C>T | intron_variant | ENST00000261275.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NSMCE3 | ENST00000332303.6 | c.626C>T | p.Pro209Leu | missense_variant | 1/1 | NM_138704.4 | P1 | ||
ENTREP2 | ENST00000261275.5 | c.277-16602C>T | intron_variant | 5 | NM_015307.2 | P1 | |||
ENTREP2 | ENST00000560082.1 | c.-12-16602C>T | intron_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74308
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Lung damage, immunodeficiency and chromosome breakage syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | in vitro;in vivo;research | Sharon E. Plon Laboratory, Baylor College of Medicine | Mar 17, 2016 | Four siblings from two unrelated kindreds died during infancy with markedly similar medical problems including severe pulmonary disease following viral pneumonia with evidence of combined T- and B-cell immunodeficiency. Chromosomal testing showed signs of increased aneuploidy/breakage. Cells from the subjects had increased sensitivity to DNA damage. One sib pair harbored rare (p.Leu264Phe) and novel (p.Pro209Leu) compound heterozygous missense variants in NSMCE3, while the other sib pair was homozygous for the p.Leu264Phe variant in NSMCE3. - |
Lung disease, immunodeficiency, and chromosome breakage syndrome; Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 19, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Benign
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Gain of MoRF binding (P = 0.0346);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at