Variant X-150470001-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005491.5(MAMLD1):c.428C>T(p.Ser143Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000895 in 111,697 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Consequence

MAMLD1
NM_005491.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.41

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33591145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAMLD1	NM_005491.5 linkuse as main transcript	c.428C>T	p.Ser143Leu	missense_variant	4/8	ENST00000370401.7	NP_005482.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAMLD1	ENST00000370401.7 linkuse as main transcript	c.428C>T	p.Ser143Leu	missense_variant	4/8	5	NM_005491.5	ENSP00000359428	A2	Q13495-1

Frequencies

GnomAD3 genomes

AF:

0.00000895

AC:

AN:

111697

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33871

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000947

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000895

AC:

AN:

111697

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33871

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000947

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 15, 2024

The c.428C>T (p.S143L) alteration is located in exon 3 (coding exon 3) of the MAMLD1 gene. This alteration results from a C to T substitution at nucleotide position 428, causing the serine (S) at amino acid position 143 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;.;.;T

FATHMM_MKL

Benign

0.48

LIST_S2

Uncertain

0.93

.;D;D;D

M_CAP

Pathogenic

0.77

MetaRNN

Benign

0.34

T;T;T;T

MetaSVM

Uncertain

-0.26

MutationAssessor

Uncertain

2.5

M;.;.;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.6

D;N;D;D

REVEL

Benign

0.25

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.012

D;D;D;D

Polyphen

0.47

P;P;B;P

Vest4

0.16

MutPred

0.29

Loss of glycosylation at S143 (P = 0.0224);.;.;Loss of glycosylation at S143 (P = 0.0224);

MVP

0.67

MPC

0.41

ClinPred

0.95

GERP RS

5.4

Varity_R

0.22

gMVP

0.62

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