rs574981584
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS2
The NM_133433.4(NIPBL):c.1583C>T(p.Thr528Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,613,674 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T528S) has been classified as Uncertain significance.
Frequency
Consequence
NM_133433.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NIPBL | NM_133433.4 | c.1583C>T | p.Thr528Met | missense_variant | 10/47 | ENST00000282516.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NIPBL | ENST00000282516.13 | c.1583C>T | p.Thr528Met | missense_variant | 10/47 | 1 | NM_133433.4 | P1 | |
NIPBL | ENST00000448238.2 | c.1583C>T | p.Thr528Met | missense_variant | 10/46 | 1 | |||
NIPBL | ENST00000652901.1 | c.1583C>T | p.Thr528Met | missense_variant | 10/46 | ||||
NIPBL | ENST00000504430.5 | n.1203C>T | non_coding_transcript_exon_variant | 6/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151990Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251170Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135756
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461566Hom.: 1 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727112
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74378
ClinVar
Submissions by phenotype
Cornelia de Lange syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2021 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 11, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at