rs2179575

Positions:

• chrX-150425249-G-C
• chrX-150425249-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005491.5(MAMLD1):​c.-63-20205G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0721 in 110,683 control chromosomes in the GnomAD database, including 383 homozygotes. There are 2,225 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 0.072 (383 hom., 2225 hem., cov: 23)
• Consequence: MAMLD1 NM_005491.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.343

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAMLD1	NM_005491.5	c.-63-20205G>C		intron_variant		ENST00000370401.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAMLD1	ENST00000370401.7	c.-63-20205G>C		intron_variant		5	NM_005491.5	A2

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 7967 AN: 110627 Hom.: 381 Cov.: 23 AF XY: 0.0673 AC XY: 2215 AN XY: 32905

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.00586

Gnomad AMR AF: 0.0645

Gnomad ASJ AF: 0.0327

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0760

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.0168

Gnomad NFE AF: 0.0257

Gnomad OTH AF: 0.0642

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

GnomAD4 genome AF: 0.0721 AC: 7985 AN: 110683 Hom.: 383 Cov.: 23 AF XY: 0.0675 AC XY: 2225 AN XY: 32971

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.0649

Gnomad4 ASJ AF: 0.0327

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0762

Gnomad4 FIN AF: 0.0213

Gnomad4 NFE AF: 0.0257

Gnomad4 OTH AF: 0.0647

Alfa AF: 0.0529 Hom.: 264

Bravo AF: 0.0829

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2179575; hg19: chrX-149593525;