rs5925535

Variant names:

• chrX-150371315-T-C
• rs5925535
• NM_005491.5:c.-64+7785T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005491.5(MAMLD1):​c.-64+7785T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 109,765 control chromosomes in the GnomAD database, including 9,177 homozygotes. There are 15,091 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (9177 hom., 15091 hem., cov: 22)
• Consequence: MAMLD1 NM_005491.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAMLD1	NM_005491.5	c.-64+7785T>C		intron_variant	Intron 1 of 7	ENST00000370401.7	NP_005482.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAMLD1	ENST00000370401.7	c.-64+7785T>C		intron_variant	Intron 1 of 7	5	NM_005491.5	ENSP00000359428.2

Frequencies

GnomAD3 genomes AF: 0.477 AC: 52375 AN: 109708 Hom.: 9179 Cov.: 22

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.578

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.466

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.477 AC: 52383 AN: 109765 Hom.: 9177 Cov.: 22 AF XY: 0.470 AC XY: 15091 AN XY: 32115

African (AFR) AF: 0.375 AC: 11323 AN: 30209

American (AMR) AF: 0.366 AC: 3776 AN: 10305

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 1554 AN: 2633

East Asian (EAS) AF: 0.424 AC: 1461 AN: 3443

South Asian (SAS) AF: 0.543 AC: 1378 AN: 2540

European-Finnish (FIN) AF: 0.596 AC: 3348 AN: 5620

Middle Eastern (MID) AF: 0.569 AC: 123 AN: 216

European-Non Finnish (NFE) AF: 0.537 AC: 28279 AN: 52637

Other (OTH) AF: 0.467 AC: 697 AN: 1492

Alfa AF: 0.510 Hom.: 72042

Bravo AF: 0.454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.3
DANN	Benign	0.78
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs5925535; hg19: chrX-149539583;