X-150470119-G-T

Position:

• chrX-150470119-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005491.5(MAMLD1):​c.546G>T​(p.Glu182Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: MAMLD1 NM_005491.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAMLD1	NM_005491.5	c.546G>T	p.Glu182Asp	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	c.546G>T	p.Glu182Asp	missense_variant	4/8	5	NM_005491.5	ENSP00000359428.2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.546G>T (p.E182D) alteration is located in exon 3 (coding exon 3) of the MAMLD1 gene. This alteration results from a G to T substitution at nucleotide position 546, causing the glutamic acid (E) at amino acid position 182 to be replaced by an aspartic acid (D). 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	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D;.;.;D
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	.;D;D;D
M_CAP	Pathogenic	0.60	D
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Pathogenic	3.0	M;.;.;M
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.9	D;D;D;D
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Benign	0.16	T;T;T;T
Polyphen		1.0	D;D;D;D
Vest4		0.70
MutPred		0.33		Loss of methylation at K185 (P = 0.1648);.;.;Loss of methylation at K185 (P = 0.1648);
MVP		0.61
MPC		0.68
ClinPred		0.99	D
GERP RS		1.6
Varity_R		0.84
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-149638391;