X-150474583-C-T

Variant names:

• chrX-150474583-C-T
• rs1209026
• NM_005491.5:c.2040+781C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005491.5(MAMLD1):​c.2040+781C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.80 (25048 hom., 26586 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: MAMLD1 NM_005491.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005491.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAMLD1	NM_005491.5	MANE Select	c.2040+781C>T		intron	N/A	NP_005482.2	Q13495-1
	MAMLD1	NM_001400512.1		c.1917+3093C>T		intron	N/A	NP_001387441.1	A0A804HKM8
	MAMLD1	NM_001177465.3		c.1842+3093C>T		intron	N/A	NP_001170936.1	Q13495-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAMLD1	ENST00000370401.7	TSL:5 MANE Select	c.2040+781C>T		intron	N/A	ENSP00000359428.2	Q13495-1
	MAMLD1	ENST00000426613.5	TSL:1	c.1965+781C>T		intron	N/A	ENSP00000397438.2	Q13495-4
	MAMLD1	ENST00000682016.1		c.1917+3093C>T		intron	N/A	ENSP00000507991.1	A0A804HKM8

Frequencies

GnomAD3 genomes AF: 0.800 AC: 88460 AN: 110618 Hom.: 25056 Cov.: 23

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.952

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.860

Gnomad NFE AF: 0.850

Gnomad OTH AF: 0.804

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.799 AC: 88470 AN: 110671 Hom.: 25048 Cov.: 23 AF XY: 0.808 AC XY: 26586 AN XY: 32913

African (AFR) AF: 0.645 AC: 19553 AN: 30335

American (AMR) AF: 0.846 AC: 8852 AN: 10465

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2215 AN: 2640

East Asian (EAS) AF: 0.952 AC: 3336 AN: 3505

South Asian (SAS) AF: 0.956 AC: 2473 AN: 2588

European-Finnish (FIN) AF: 0.879 AC: 5173 AN: 5887

Middle Eastern (MID) AF: 0.851 AC: 183 AN: 215

European-Non Finnish (NFE) AF: 0.850 AC: 44920 AN: 52834

Other (OTH) AF: 0.807 AC: 1229 AN: 1523

Alfa AF: 0.815 Hom.: 15523

Bravo AF: 0.791

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.53
PhyloP100		-0.54

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1209026; hg19: chrX-149642855;