Variant rs2073043 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.1985A>G(p.Asn662Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,202,243 control chromosomes in the GnomAD database, including 7,994 homozygotes. There are 51,547 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/16 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 0.10 ( 583 hom., 3233 hem., cov: 23)

Exomes 𝑓: 0.14 ( 7411 hom. 48314 hem. )

Consequence

MAMLD1
NM_005491.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.441

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=0.0011407137).

BP6

Variant X-150473747-A-G is Benign according to our data. Variant chrX-150473747-A-G is described in ClinVar as [Benign]. Clinvar id is 1598681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 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.1985A>G	p.Asn662Ser	missense_variant	5/8	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.1985A>G	p.Asn662Ser	missense_variant	5/8	5	NM_005491.5	ENSP00000359428.2		Q13495-1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

11515

AN:

110226

Hom.:

581

Cov.:

AF XY:

0.0988

AC XY:

3231

AN XY:

32696

show subpopulations

Gnomad AFR

AF:

0.0264

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.0517

Gnomad SAS

AF:

0.0400

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.106

GnomAD3 exomes

AF:

0.110

AC:

20147

AN:

183205

Hom.:

799

AF XY:

0.112

AC XY:

7549

AN XY:

67671

show subpopulations

Gnomad AFR exome

AF:

0.0233

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.0573

Gnomad SAS exome

AF:

0.0491

Gnomad FIN exome

AF:

0.125

Gnomad NFE exome

AF:

0.142

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.136

AC:

148987

AN:

1091963

Hom.:

7411

Cov.:

AF XY:

0.135

AC XY:

48314

AN XY:

357593

show subpopulations

Gnomad4 AFR exome

AF:

0.0244

Gnomad4 AMR exome

AF:

0.102

Gnomad4 ASJ exome

AF:

0.159

Gnomad4 EAS exome

AF:

0.0541

Gnomad4 SAS exome

AF:

0.0527

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.150

Gnomad4 OTH exome

AF:

0.126

GnomAD4 genome

AF:

0.104

AC:

11515

AN:

110280

Hom.:

583

Cov.:

AF XY:

0.0987

AC XY:

3233

AN XY:

32760

show subpopulations

Gnomad4 AFR

AF:

0.0263

Gnomad4 AMR

AF:

0.112

Gnomad4 ASJ

AF:

0.155

Gnomad4 EAS

AF:

0.0519

Gnomad4 SAS

AF:

0.0405

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.149

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.126

Hom.:

2901

Bravo

AF:

0.102

TwinsUK

AF:

0.148

AC:

549

ALSPAC

AF:

0.144

AC:

417

ESP6500AA

AF:

0.0300

AC:

115

ESP6500EA

AF:

0.145

AC:

976

ExAC

AF:

0.110

AC:

13328

EpiCase

AF:

0.144

EpiControl

AF:

0.142

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	Jan 25, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.3

DANN

Benign

0.94

DEOGEN2

Benign

0.040

T;.;T

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.61

.;T;T

MetaRNN

Benign

0.0011

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.;L

PROVEAN

Benign

-0.45

N;N;N

REVEL

Benign

0.032

Sift

Benign

0.039

D;D;D

Sift4G

Benign

0.65

T;T;T

Polyphen

0.34

B;B;B

Vest4

0.025

ClinPred

0.0038

GERP RS

2.5

Varity_R

0.053

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