Variant 7-4920258-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198403.4(MMD2):c.203C>G(p.Ser68Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,603,896 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: 0.000012 ( 0 hom. )

Consequence

MMD2
NM_198403.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.43

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:

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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/exons	MANE	Protein
MMD2	NM_198403.4 linkuse as main transcript	c.203C>G	p.Ser68Cys	missense_variant	3/7	ENST00000401401.8	NP_940685.3
MMD2	NM_001100600.2 linkuse as main transcript	c.203C>G	p.Ser68Cys	missense_variant	3/7		NP_001094070.1
MMD2	NM_001270375.2 linkuse as main transcript	c.203C>G	p.Ser68Cys	missense_variant	3/8		NP_001257304.1
MMD2	NR_072989.2 linkuse as main transcript	n.373C>G		non_coding_transcript_exon_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMD2	ENST00000401401.8 linkuse as main transcript	c.203C>G	p.Ser68Cys	missense_variant	3/7	1	NM_198403.4	ENSP00000384141	P1	Q8IY49-2
MMD2	ENST00000404774.7 linkuse as main transcript	c.203C>G	p.Ser68Cys	missense_variant	3/7	1		ENSP00000384690		Q8IY49-1
MMD2	ENST00000406755.5 linkuse as main transcript	c.203C>G	p.Ser68Cys	missense_variant	3/8	1		ENSP00000385963		Q8IY49-3
MMD2	ENST00000612910.1 linkuse as main transcript	c.203C>G	p.Ser68Cys	missense_variant	3/7	5		ENSP00000484193		Q8IY49-3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000866

AC:

AN:

230990

Hom.:

AF XY:

0.00000801

AC XY:

AN XY:

124904

show subpopulations

Gnomad AFR exome

AF:

0.0000724

Gnomad AMR exome

AF:

0.00

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:

0.00000954

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1451650

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

720898

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:

0.0000153

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.000239

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000826

AC:

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

Apr 19, 2023

The c.203C>G (p.S68C) alteration is located in exon 3 (coding exon 3) of the MMD2 gene. This alteration results from a C to G substitution at nucleotide position 203, causing the serine (S) at amino acid position 68 to be replaced by a cysteine (C). 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

0.18

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.21

.;T;.;.

Eigen

Benign

0.032

Eigen_PC

Benign

0.087

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.91

.;D;D;D

M_CAP

Benign

0.0047

MetaRNN

Uncertain

0.59

D;D;D;D

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.5

M;M;M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.0

D;D;D;.

REVEL

Benign

0.18

Sift

Benign

0.070

T;T;T;.

Sift4G

Uncertain

0.045

D;T;T;D

Polyphen

0.12, 0.084

.;B;B;.

Vest4

0.77

MVP

0.47

MPC

0.055

ClinPred

0.61

GERP RS

4.4

Varity_R

0.24

gMVP

0.89

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