7-4916057-T-C

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198403.4(MMD2):c.313A>G(p.Met105Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,630 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

MMD2
NM_198403.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86

Variant links:

Genes affected

MMD2 (HGNC:30133): (monocyte to macrophage differentiation associated 2) This gene encodes a member of the PAQR (progestin and adipoQ receptor) family. Members of this family are evolutionarily conserved with significant sequence identity to bacterial hemolysin-like proteins and are defined by a set of seven transmembrane domains. The protein encoded by this gene localizes to the Golgi apparatus to modulate Ras signaling. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jun 2012]

MMD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMD2	NM_198403.4 link	c.313A>G	p.Met105Val	missense_variant	Exon 4 of 7	ENST00000401401.8	NP_940685.3	Q8IY49-2
MMD2	NM_001100600.2 link	c.313A>G	p.Met105Val	missense_variant	Exon 4 of 7		NP_001094070.1	Q8IY49-1
MMD2	NM_001270375.2 link	c.313A>G	p.Met105Val	missense_variant	Exon 4 of 8		NP_001257304.1	Q8IY49-3
MMD2	NR_072989.2 link	n.483A>G		non_coding_transcript_exon_variant	Exon 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MMD2	ENST00000401401.8 link	c.313A>G	p.Met105Val	missense_variant	Exon 4 of 7	1	NM_198403.4	ENSP00000384141.3	Q8IY49-2
MMD2	ENST00000404774.7 link	c.313A>G	p.Met105Val	missense_variant	Exon 4 of 7	1		ENSP00000384690.3	Q8IY49-1
MMD2	ENST00000406755.5 link	c.313A>G	p.Met105Val	missense_variant	Exon 4 of 8	1		ENSP00000385963.1	Q8IY49-3
MMD2	ENST00000612910.1 link	c.313A>G	p.Met105Val	missense_variant	Exon 4 of 7	5			Q8IY49-3

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

249014

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135184

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461564

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.313A>G (p.M105V) alteration is located in exon 4 (coding exon 4) of the MMD2 gene. This alteration results from a A to G substitution at nucleotide position 313, causing the methionine (M) at amino acid position 105 to be replaced by a valine (V). 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

Benign

0.21

BayesDel_addAF

Uncertain

0.030

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.064

.;T;.;.

Eigen

Benign

-0.046

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

.;D;D;D

M_CAP

Benign

0.0077

MetaRNN

Uncertain

0.58

D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.27

N;N;N;N

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.5

D;D;D;.

REVEL

Uncertain

0.30

Sift

Benign

0.21

T;T;T;.

Sift4G

Benign

0.68

T;T;T;T

Polyphen

0.20, 0.021

.;B;B;.

Vest4

0.63

MutPred

0.76

Gain of catalytic residue at M105 (P = 0.0752);Gain of catalytic residue at M105 (P = 0.0752);Gain of catalytic residue at M105 (P = 0.0752);Gain of catalytic residue at M105 (P = 0.0752);

MVP

0.19

MPC

0.042

ClinPred

0.51

GERP RS

4.6

Varity_R

0.32

gMVP

0.69

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

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