chr7-4920326-C-A

Position:

chr7-4920326-C-A

Variant summary

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

The ENST00000401401.8(MMD2):c.135G>T(p.Trp45Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000535 in 1,607,754 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

MMD2
ENST00000401401.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.46

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:

MMD2 (HGNC:):

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	UniProt
MMD2	NM_198403.4 linkuse as main transcript	c.135G>T	p.Trp45Cys	missense_variant	3/7	ENST00000401401.8	NP_940685.3	Q8IY49-2
MMD2	NM_001100600.2 linkuse as main transcript	c.135G>T	p.Trp45Cys	missense_variant	3/7		NP_001094070.1	Q8IY49-1
MMD2	NM_001270375.2 linkuse as main transcript	c.135G>T	p.Trp45Cys	missense_variant	3/8		NP_001257304.1	Q8IY49-3
MMD2	NR_072989.2 linkuse as main transcript	n.305G>T		non_coding_transcript_exon_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MMD2	ENST00000401401.8 linkuse as main transcript	c.135G>T	p.Trp45Cys	missense_variant	3/7	1	NM_198403.4	ENSP00000384141.3	Q8IY49-2
MMD2	ENST00000404774.7 linkuse as main transcript	c.135G>T	p.Trp45Cys	missense_variant	3/7	1		ENSP00000384690.3	Q8IY49-1
MMD2	ENST00000406755.5 linkuse as main transcript	c.135G>T	p.Trp45Cys	missense_variant	3/8	1		ENSP00000385963.1	Q8IY49-3
MMD2	ENST00000612910.1 linkuse as main transcript	c.135G>T	p.Trp45Cys	missense_variant	3/7	5			Q8IY49-3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152218

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000298

AC:

AN:

234962

Hom.:

AF XY:

0.0000236

AC XY:

AN XY:

127230

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000654

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000570

AC:

AN:

1455536

Hom.:

Cov.:

AF XY:

0.0000456

AC XY:

AN XY:

723202

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000378

Gnomad4 NFE exome

AF:

0.0000694

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152218

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000284

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000579

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

Nov 06, 2023

The c.135G>T (p.W45C) alteration is located in exon 3 (coding exon 3) of the MMD2 gene. This alteration results from a G to T substitution at nucleotide position 135, causing the tryptophan (W) at amino acid position 45 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

Uncertain

0.36

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

.;T;.;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.89

.;D;D;D

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.70

D;D;D;D

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.8

L;L;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-8.1

D;D;D;.

REVEL

Uncertain

0.33

Sift

Benign

0.042

D;D;T;.

Sift4G

Uncertain

0.040

D;T;T;D

Polyphen

0.37, 0.14

.;B;B;.

Vest4

0.86

MutPred

0.74

Loss of glycosylation at S49 (P = 0.2642);Loss of glycosylation at S49 (P = 0.2642);Loss of glycosylation at S49 (P = 0.2642);Loss of glycosylation at S49 (P = 0.2642);

MVP

0.22

MPC

0.11

ClinPred

0.93

GERP RS

4.4

Varity_R

0.76

gMVP

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.49

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.49

Position offset: -12

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