Variant 17-55421687-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012329.3(MMD):c.9C>A(p.Phe3Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000235 in 1,444,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

MMD
NM_012329.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.51

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06922096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMD	NM_012329.3 linkuse as main transcript	c.9C>A	p.Phe3Leu	missense_variant	1/7	ENST00000262065.8	NP_036461.2
MMD	XM_047435708.1 linkuse as main transcript	c.9C>A	p.Phe3Leu	missense_variant	1/5		XP_047291664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MMD	ENST00000262065.8 linkuse as main transcript	c.9C>A	p.Phe3Leu	missense_variant	1/7	1	NM_012329.3	ENSP00000262065	P1
MMD	ENST00000649377.1 linkuse as main transcript	c.9C>A	p.Phe3Leu	missense_variant	1/8			ENSP00000497849
MMD	ENST00000571578.1 linkuse as main transcript	c.9C>A	p.Phe3Leu	missense_variant	1/5	3		ENSP00000459202
MMD	ENST00000577038.1 linkuse as main transcript	n.111C>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000235

AC:

AN:

1444230

Hom.:

Cov.:

AF XY:

0.0000223

AC XY:

AN XY:

718630

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000308

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000318

Hom.:

Bravo

AF:

0.00000756

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

Mar 25, 2024

The c.9C>A (p.F3L) alteration is located in exon 1 (coding exon 1) of the MMD gene. This alteration results from a C to A substitution at nucleotide position 9, causing the phenylalanine (F) at amino acid position 3 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.18

T;.;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.069

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.46

N;.;.

MutationTaster

Benign

0.55

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.16

N;.;.

REVEL

Benign

0.14

Sift

Benign

1.0

T;.;.

Sift4G

Benign

1.0

T;.;T

Polyphen

0.0

B;.;.

Vest4

0.33

MutPred

0.19

Loss of methylation at K4 (P = 0.0369);Loss of methylation at K4 (P = 0.0369);Loss of methylation at K4 (P = 0.0369);

MVP

0.25

MPC

0.77

ClinPred

0.37

GERP RS

4.6

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)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over