rs5925535

Positions:

• chrX-150371315-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
MAMLD1	NM_005491.5	c.-64+7785T>C		intron_variant		ENST00000370401.7	NP_005482.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAMLD1	ENST00000370401.7	c.-64+7785T>C		intron_variant		5	NM_005491.5	ENSP00000359428.2

Frequencies

GnomAD3 genomes AF: 0.477 AC: 52375 AN: 109708 Hom.: 9179 Cov.: 22 AF XY: 0.470 AC XY: 15076 AN XY: 32048

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

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.467

Alfa AF: 0.525 Hom.: 57168

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

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

Other links and lift over

dbSNP: rs5925535; hg19: chrX-149539583;