7-4920190-A-G

Position:

chr7-4920190-A-G

Variant summary

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

The NM_198403.4(MMD2):c.271T>C(p.Trp91Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,566,322 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

MMD2
NM_198403.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.71

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/exons	MANE	Protein
MMD2	NM_198403.4 linkuse as main transcript	c.271T>C	p.Trp91Arg	missense_variant	3/7	ENST00000401401.8	NP_940685.3
MMD2	NM_001100600.2 linkuse as main transcript	c.271T>C	p.Trp91Arg	missense_variant	3/7		NP_001094070.1
MMD2	NM_001270375.2 linkuse as main transcript	c.271T>C	p.Trp91Arg	missense_variant	3/8		NP_001257304.1
MMD2	NR_072989.2 linkuse as main transcript	n.441T>C		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.271T>C	p.Trp91Arg	missense_variant	3/7	1	NM_198403.4	ENSP00000384141	P1	Q8IY49-2
MMD2	ENST00000404774.7 linkuse as main transcript	c.271T>C	p.Trp91Arg	missense_variant	3/7	1		ENSP00000384690		Q8IY49-1
MMD2	ENST00000406755.5 linkuse as main transcript	c.271T>C	p.Trp91Arg	missense_variant	3/8	1		ENSP00000385963		Q8IY49-3
MMD2	ENST00000612910.1 linkuse as main transcript	c.271T>C	p.Trp91Arg	missense_variant	3/7	5		ENSP00000484193		Q8IY49-3

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000279

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000120

AC:

AN:

175112

Hom.:

AF XY:

0.000139

AC XY:

AN XY:

93556

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000384

Gnomad ASJ exome

AF:

0.000114

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000258

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000168

AC:

238

AN:

1413984

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

112

AN XY:

698826

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000541

Gnomad4 ASJ exome

AF:

0.0000395

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000207

Gnomad4 OTH exome

AF:

0.000136

GnomAD4 genome

AF:

0.000151

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000222

Hom.:

Bravo

AF:

0.000155

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.000143

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

Oct 05, 2022

The c.271T>C (p.W91R) alteration is located in exon 3 (coding exon 3) of the MMD2 gene. This alteration results from a T to C substitution at nucleotide position 271, causing the tryptophan (W) at amino acid position 91 to be replaced by an arginine (R). 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

Pathogenic

0.99

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

.;T;.;.

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

.;D;D;D

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.74

D;D;D;D

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.6

L;L;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-8.8

D;D;D;.

REVEL

Uncertain

0.37

Sift

Uncertain

0.0010

D;T;D;.

Sift4G

Benign

0.13

T;T;T;T

Polyphen

1.0, 1.0

.;D;D;.

Vest4

0.93

MutPred

0.63

Gain of disorder (P = 7e-04);Gain of disorder (P = 7e-04);Gain of disorder (P = 7e-04);Gain of disorder (P = 7e-04);

MVP

0.51

MPC

0.33

ClinPred

0.83

GERP RS

4.3

Varity_R

0.73

gMVP

0.91

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