Variant X-150462831-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005491.5(MAMLD1):c.156A>G(p.Pro52=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,206,952 control chromosomes in the GnomAD database, including 47 homozygotes. There are 825 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 17 hom., 370 hem., cov: 23)

Exomes 𝑓: 0.0016 ( 30 hom. 455 hem. )

Consequence

MAMLD1
NM_005491.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.138

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant X-150462831-A-G is Benign according to our data. Variant chrX-150462831-A-G is described in ClinVar as [Benign]. Clinvar id is 714971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.138 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0129 (1450/112309) while in subpopulation AFR AF= 0.0439 (1354/30874). AF 95% confidence interval is 0.0419. There are 17 homozygotes in gnomad4. There are 370 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAMLD1	NM_005491.5 linkuse as main transcript	c.156A>G	p.Pro52=	synonymous_variant	3/8	ENST00000370401.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAMLD1	ENST00000370401.7 linkuse as main transcript	c.156A>G	p.Pro52=	synonymous_variant	3/8	5	NM_005491.5	A2	Q13495-1

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1453

AN:

112255

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

371

AN XY:

34411

show subpopulations

Gnomad AFR

AF:

0.0441

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000326

Gnomad MID

AF:

0.00837

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00925

GnomAD3 exomes

AF:

0.00392

AC:

711

AN:

181375

Hom.:

AF XY:

0.00227

AC XY:

153

AN XY:

67257

show subpopulations

Gnomad AFR exome

AF:

0.0502

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000211

Gnomad FIN exome

AF:

0.000628

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.00269

GnomAD4 exome

AF:

0.00156

AC:

1712

AN:

1094643

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

455

AN XY:

360091

show subpopulations

Gnomad4 AFR exome

AF:

0.0485

Gnomad4 AMR exome

AF:

0.00236

Gnomad4 ASJ exome

AF:

0.0000517

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000241

Gnomad4 FIN exome

AF:

0.000815

Gnomad4 NFE exome

AF:

0.000184

Gnomad4 OTH exome

AF:

0.00311

GnomAD4 genome

AF:

0.0129

AC:

1450

AN:

112309

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

370

AN XY:

34475

show subpopulations

Gnomad4 AFR

AF:

0.0439

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000326

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00914

Alfa

AF:

0.00738

Hom.:

Bravo

AF:

0.0153

EpiCase

AF:

0.000273

EpiControl

AF:

0.00

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 25, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.3

DANN

Benign

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