rs193920839

Variant names:

• chrX-150510035-G-T
• rs193920839
• ENST00000464149.1:n.711G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000464149.1(MAMLD1):​n.711G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MAMLD1 ENST00000464149.1 non_coding_transcript_exon
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.25
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hypospadias 2, X-linked

  Inheritance: XL Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21000901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAMLD1	NM_005491.5	c.*33G>T		3_prime_UTR_variant	Exon 7 of 8	ENST00000370401.7	NP_005482.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAMLD1	ENST00000370401.7	c.*33G>T		3_prime_UTR_variant	Exon 7 of 8	5	NM_005491.5	ENSP00000359428.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer Uncertain:1

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Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	12
DANN	Uncertain	1.0
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.94	T
PhyloP100		1.3
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.20
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.20	T
Polyphen		0.81	P
Vest4		0.40
MutPred		0.40		Gain of catalytic residue at S639 (P = 0.0124);
MVP		0.093
MPC		0.31
ClinPred		0.74	D
GERP RS		1.8
gMVP		0.42
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs193920839; hg19: chrX-149678305; COSMIC: COSV53381637;