X-150447931-A-G

Variant names:

• chrX-150447931-A-G
• rs611711
• NM_005491.5:c.96+2319A>G

Variant summary

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

The NM_005491.5(MAMLD1):​c.96+2319A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 111,157 control chromosomes in the GnomAD database, including 6,776 homozygotes. There are 13,542 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 0.40 (6776 hom., 13542 hem., cov: 23)
• Consequence: MAMLD1 NM_005491.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

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.96+2319A>G		intron	N/A	NP_005482.2	Q13495-1
	MAMLD1	NM_001400512.1		c.96+2319A>G		intron	N/A	NP_001387441.1	A0A804HKM8
	MAMLD1	NM_001177465.3		c.96+2319A>G		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.96+2319A>G		intron	N/A	ENSP00000359428.2	Q13495-1
	MAMLD1	ENST00000426613.5	TSL:1	c.96+2319A>G		intron	N/A	ENSP00000397438.2	Q13495-4
	MAMLD1	ENST00000682016.1		c.96+2319A>G		intron	N/A	ENSP00000507991.1	A0A804HKM8

Frequencies

GnomAD3 genomes AF: 0.403 AC: 44737 AN: 111102 Hom.: 6770 Cov.: 23

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.403 AC: 44760 AN: 111157 Hom.: 6776 Cov.: 23 AF XY: 0.405 AC XY: 13542 AN XY: 33403

African (AFR) AF: 0.443 AC: 13526 AN: 30506

American (AMR) AF: 0.559 AC: 5869 AN: 10506

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 704 AN: 2636

East Asian (EAS) AF: 0.800 AC: 2820 AN: 3523

South Asian (SAS) AF: 0.454 AC: 1202 AN: 2649

European-Finnish (FIN) AF: 0.373 AC: 2226 AN: 5973

Middle Eastern (MID) AF: 0.272 AC: 59 AN: 217

European-Non Finnish (NFE) AF: 0.329 AC: 17424 AN: 52948

Other (OTH) AF: 0.402 AC: 615 AN: 1530

Alfa AF: 0.370 Hom.: 38765

Bravo AF: 0.430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
PhyloP100		-0.034

Splicing

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

Other links and lift over

dbSNP: rs611711; hg19: chrX-149616197;