Variant X-150469782-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_005491.5(MAMLD1):c.209A>G(p.Gln70Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,208,505 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 41 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000081 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.00011 ( 0 hom. 40 hem. )

Consequence

MAMLD1
NM_005491.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.743

Variant links:

Genes affected

MAMLD1 (HGNC:2568): (mastermind like domain containing 1) This gene encodes a mastermind-like domain containing protein. This protein may function as a transcriptional co-activator. Mutations in this gene are the cause of X-linked hypospadias type 2. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

MAMLD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07210541).

BP6

Variant X-150469782-A-G is Benign according to our data. Variant chrX-150469782-A-G is described in ClinVar as [Benign]. Clinvar id is 1621919.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-150469782-A-G is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAdExome4 at 40 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAMLD1	NM_005491.5 linkuse as main transcript	c.209A>G	p.Gln70Arg	missense_variant	4/8	ENST00000370401.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAMLD1	ENST00000370401.7 linkuse as main transcript	c.209A>G	p.Gln70Arg	missense_variant	4/8	5	NM_005491.5	A2	Q13495-1

Frequencies

GnomAD3 genomes

AF:

0.0000814

AC:

AN:

110519

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

32739

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000170

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000766

AC:

AN:

182684

Hom.:

AF XY:

0.0000593

AC XY:

AN XY:

67414

show subpopulations

Gnomad AFR exome

AF:

0.0000769

Gnomad AMR exome

AF:

0.0000365

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:

0.000147

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000115

AC:

126

AN:

1097986

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

363354

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

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:

0.000138

Gnomad4 OTH exome

AF:

0.000195

GnomAD4 genome

AF:

0.0000814

AC:

AN:

110519

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

32739

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000170

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 10, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

T;.;T;.;T

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.69

.;T;T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.072

T;T;T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.5

M;.;.;.;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.4

N;N;N;N;N

REVEL

Benign

0.21

Sift

Benign

0.83

T;T;T;T;T

Sift4G

Benign

0.42

T;T;T;T;T

Polyphen

0.90

P;B;.;P;P

Vest4

0.17

MVP

0.75

MPC

0.20

ClinPred

0.39

GERP RS

3.4

Varity_R

0.14

gMVP

0.33

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