Variant X-150470078-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005491.5(MAMLD1):c.505G>A(p.Val169Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,209,818 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000013 ( 0 hom. 2 hem. )

Consequence

MAMLD1
NM_005491.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.26

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019603968).

BP6

Variant X-150470078-G-A is Benign according to our data. Variant chrX-150470078-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2956289.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAMLD1	NM_005491.5 linkuse as main transcript	c.505G>A	p.Val169Met	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.505G>A	p.Val169Met	missense_variant	4/8	5	NM_005491.5	A2	Q13495-1

Frequencies

GnomAD3 genomes

AF:

0.00000895

AC:

AN:

111717

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33897

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000218

AC:

AN:

183272

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

67760

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000127

AC:

AN:

1098101

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363455

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.00000831

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000895

AC:

AN:

111717

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33897

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:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000567

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.86

Cadd

Benign

0.0020

Dann

Benign

0.087

DEOGEN2

Benign

0.020

T;.;.;T

FATHMM_MKL

Benign

0.013

M_CAP

Benign

0.015

MetaRNN

Benign

0.020

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.18

N;.;.;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.29

N;N;N;N

REVEL

Benign

0.012

Sift

Benign

0.57

T;T;T;T

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.14

B;B;B;B

Vest4

0.099

MVP

0.28

MPC

0.19

ClinPred

0.013

GERP RS

-11

Varity_R

0.030

gMVP

0.20

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