chr10-97462088-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_022362.5(MMS19):c.2044C>T(p.Pro682Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000267 in 1,585,956 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 1 hom. )
Consequence
MMS19
NM_022362.5 missense
NM_022362.5 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 3.93
Genes affected
MMS19 (HGNC:13824): (MMS19 homolog, cytosolic iron-sulfur assembly component) Enables estrogen receptor binding activity and transcription coactivator activity. Involved in several processes, including iron-sulfur cluster assembly; positive regulation of nucleobase-containing compound metabolic process; and protein maturation by iron-sulfur cluster transfer. Located in cytosol; nucleoplasm; and spindle. Part of CIA complex and MMXD complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.06002766).
BS2
?
High AC in GnomAd at 24 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MMS19 | NM_022362.5 | c.2044C>T | p.Pro682Ser | missense_variant | 21/31 | ENST00000438925.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MMS19 | ENST00000438925.7 | c.2044C>T | p.Pro682Ser | missense_variant | 21/31 | 1 | NM_022362.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152232Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000121 AC: 25AN: 207416Hom.: 0 AF XY: 0.0000996 AC XY: 11AN XY: 110402
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GnomAD4 exome AF: 0.000278 AC: 399AN: 1433606Hom.: 1 Cov.: 31 AF XY: 0.000259 AC XY: 184AN XY: 710310
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GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152350Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74498
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2021 | The c.2044C>T (p.P682S) alteration is located in exon 21 (coding exon 21) of the MMS19 gene. This alteration results from a C to T substitution at nucleotide position 2044, causing the proline (P) at amino acid position 682 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;B;B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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