Variant chr9-136853335-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000317446.7(MAMDC4):c.205G>A(p.Glu69Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000167 in 1,606,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

MAMDC4
ENST00000317446.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.03

Variant links:

Genes affected

MAMDC4 (HGNC:24083): (MAM domain containing 4) Predicted to be involved in protein transport. Predicted to be located in membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MAMDC4 links:

MAMDC4 (HGNC:):

MAMDC4 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=0.13035533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAMDC4	NM_206920.3 linkuse as main transcript	c.205G>A	p.Glu69Lys	missense_variant	3/27	ENST00000317446.7	NP_996803.2	Q6UXC1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAMDC4	ENST00000317446.7 linkuse as main transcript	c.205G>A	p.Glu69Lys	missense_variant	3/27	1	NM_206920.3	ENSP00000319388.2	Q6UXC1-2
MAMDC4	ENST00000485732.5 linkuse as main transcript	n.449G>A		non_coding_transcript_exon_variant	5/25	1
MAMDC4	ENST00000445819.5 linkuse as main transcript	c.205G>A	p.Glu69Lys	missense_variant	3/29	5		ENSP00000411339.1	Q6UXC1-1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000325

AC:

AN:

246158

Hom.:

AF XY:

0.000329

AC XY:

AN XY:

133918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000379

Gnomad ASJ exome

AF:

0.00556

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000905

Gnomad OTH exome

AF:

0.000333

GnomAD4 exome

AF:

0.000169

AC:

246

AN:

1454112

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

127

AN XY:

722174

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000405

Gnomad4 ASJ exome

AF:

0.00518

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000533

Gnomad4 OTH exome

AF:

0.000517

GnomAD4 genome

AF:

0.000145

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000318

Hom.:

Bravo

AF:

0.000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.000190

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

Feb 08, 2023

The c.205G>A (p.E69K) alteration is located in exon 3 (coding exon 3) of the MAMDC4 gene. This alteration results from a G to A substitution at nucleotide position 205, causing the glutamic acid (E) at amino acid position 69 to be replaced by a lysine (K). 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

0.53

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

.;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.082

MetaRNN

Benign

0.13

T;T

MetaSVM

Uncertain

0.45

MutationAssessor

Pathogenic

3.7

H;H

MutationTaster

Benign

0.79

D;D

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.5

D;D

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.77

MVP

0.59

MPC

0.20

ClinPred

0.75

GERP RS

4.6

Varity_R

0.81

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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