chr17-55411404-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_012329.3(MMD):c.122C>T(p.Pro41Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000379 in 1,610,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
MMD
NM_012329.3 missense
NM_012329.3 missense
Scores
7
7
5
Clinical Significance
Conservation
PhyloP100: 9.56
Genes affected
MMD (HGNC:7153): (monocyte to macrophage differentiation associated) This protein is expressed by in vitro differentiated macrophages but not freshly isolated monocytes. Although sequence analysis identifies seven potential transmembrane domains, this protein has little homology to G-protein receptors and it has not been positively identified as a receptor. A suggested alternative function is that of an ion channel protein in maturing macrophages. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.811
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MMD | NM_012329.3 | c.122C>T | p.Pro41Leu | missense_variant | 3/7 | ENST00000262065.8 | |
MMD | XM_047435708.1 | c.122C>T | p.Pro41Leu | missense_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MMD | ENST00000262065.8 | c.122C>T | p.Pro41Leu | missense_variant | 3/7 | 1 | NM_012329.3 | P1 | |
MMD | ENST00000649377.1 | c.122C>T | p.Pro41Leu | missense_variant | 3/8 | ||||
MMD | ENST00000571578.1 | c.122C>T | p.Pro41Leu | missense_variant | 3/5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152218Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000121 AC: 3AN: 247090Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133620
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GnomAD4 exome AF: 0.0000336 AC: 49AN: 1458478Hom.: 0 Cov.: 30 AF XY: 0.0000331 AC XY: 24AN XY: 725588
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GnomAD4 genome AF: 0.0000788 AC: 12AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74490
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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 | Feb 28, 2024 | The c.122C>T (p.P41L) alteration is located in exon 3 (coding exon 3) of the MMD gene. This alteration results from a C to T substitution at nucleotide position 122, causing the proline (P) at amino acid position 41 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;.
REVEL
Uncertain
Sift
Uncertain
D;.;.
Sift4G
Benign
T;.;T
Polyphen
D;.;.
Vest4
MVP
MPC
ClinPred
D
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