Variant rs41313406 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005491.5(MAMLD1):c.1075C>T(p.Pro359Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,209,970 control chromosomes in the GnomAD database, including 5,619 homozygotes. There are 42,894 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.082 ( 408 hom., 2550 hem., cov: 23)

Exomes 𝑓: 0.11 ( 5211 hom. 40344 hem. )

Consequence

MAMLD1
NM_005491.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.09

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017882288).

BP6

Variant X-150470648-C-T is Benign according to our data. Variant chrX-150470648-C-T is described in ClinVar as [Benign]. Clinvar id is 1542510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAMLD1	NM_005491.5 linkuse as main transcript	c.1075C>T	p.Pro359Ser	missense_variant	4/8	ENST00000370401.7	NP_005482.2	Q13495-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAMLD1	ENST00000370401.7 linkuse as main transcript	c.1075C>T	p.Pro359Ser	missense_variant	4/8	5	NM_005491.5	ENSP00000359428.2		Q13495-1

Frequencies

GnomAD3 genomes

AF:

0.0825

AC:

9227

AN:

111791

Hom.:

408

Cov.:

AF XY:

0.0751

AC XY:

2550

AN XY:

33969

show subpopulations

Gnomad AFR

AF:

0.0149

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.0765

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.000280

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.106

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.0885

GnomAD3 exomes

AF:

0.0829

AC:

15030

AN:

181336

Hom.:

506

AF XY:

0.0851

AC XY:

5691

AN XY:

66858

show subpopulations

Gnomad AFR exome

AF:

0.0136

Gnomad AMR exome

AF:

0.0476

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.000289

Gnomad SAS exome

AF:

0.0320

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.0967

GnomAD4 exome

AF:

0.113

AC:

123680

AN:

1098127

Hom.:

5211

Cov.:

AF XY:

0.111

AC XY:

40344

AN XY:

363487

show subpopulations

Gnomad4 AFR exome

AF:

0.0147

Gnomad4 AMR exome

AF:

0.0519

Gnomad4 ASJ exome

AF:

0.135

Gnomad4 EAS exome

AF:

0.000232

Gnomad4 SAS exome

AF:

0.0354

Gnomad4 FIN exome

AF:

0.116

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.0825

AC:

9222

AN:

111843

Hom.:

408

Cov.:

AF XY:

0.0749

AC XY:

2550

AN XY:

34031

show subpopulations

Gnomad4 AFR

AF:

0.0149

Gnomad4 AMR

AF:

0.0763

Gnomad4 ASJ

AF:

0.126

Gnomad4 EAS

AF:

0.000281

Gnomad4 SAS

AF:

0.0210

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.126

Gnomad4 OTH

AF:

0.0861

Alfa

AF:

0.119

Hom.:

5264

Bravo

AF:

0.0788

ESP6500AA

AF:

0.0177

AC:

ESP6500EA

AF:

0.126

AC:

846

ExAC

AF:

0.0841

AC:

10215

EpiCase

AF:

0.125

EpiControl

AF:

0.123

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.049

T;.;.;T

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.76

.;T;T;T

MetaRNN

Benign

0.0018

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

2.0

M;.;.;M

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.12

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Benign

0.44

T;T;T;T

Polyphen

0.78

P;B;D;P

Vest4

0.083

MPC

0.35

ClinPred

0.023

GERP RS

0.28

Varity_R

0.14

gMVP

0.47

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