Genetic Variant MMD:p.Phe3Leu (chr17-55421687-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012329.3(MMD):c.9C>G(p.Phe3Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,444,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MMD
NM_012329.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.51

Publications

0 publications found

Variant links:

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]

MMD links:

ENSG00000301916 (HGNC:):

ENSG00000301916 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07767531).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012329.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMD	NM_012329.3	MANE Select	c.9C>G	p.Phe3Leu	missense	Exon 1 of 7	NP_036461.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MMD	ENST00000262065.8	TSL:1 MANE Select	c.9C>G	p.Phe3Leu	missense	Exon 1 of 7	ENSP00000262065.3	Q15546
MMD	ENST00000649377.1		c.9C>G	p.Phe3Leu	missense	Exon 1 of 8	ENSP00000497849.1	A0A3B3ITQ3
MMD	ENST00000936217.1		c.9C>G	p.Phe3Leu	missense	Exon 1 of 7	ENSP00000606276.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1444230

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718630

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32034

American (AMR)

AF:

0.00

AC:

AN:

41852

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25554

East Asian (EAS)

AF:

0.00

AC:

AN:

37502

South Asian (SAS)

AF:

0.00

AC:

AN:

85122

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1104468

Other (OTH)

AF:

0.00

AC:

AN:

59632

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.18

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.66

M_CAP

Benign

0.013

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.46

PhyloP100

4.5

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.16

REVEL

Benign

0.21

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.33

MutPred

0.19

Loss of methylation at K4 (P = 0.0369)

MVP

0.25

MPC

0.77

ClinPred

0.44

GERP RS

4.6

PromoterAI

0.074

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.28

gMVP

0.49

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over