NM_005491.5:c.172-2716A>G

Variant names:

• chrX-150467029-A-G
• rs17252936
• NM_005491.5:c.172-2716A>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.172-2716A>G 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 0.11 (461 hom., 2112 hem., cov: 17)
• Consequence: MAMLD1 NM_005491.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.468
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 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.172-2716A>G		intron	N/A	NP_005482.2	Q13495-1
	MAMLD1	NM_001400512.1		c.172-2716A>G		intron	N/A	NP_001387441.1	A0A804HKM8
	MAMLD1	NM_001177465.3		c.97-2716A>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.172-2716A>G		intron	N/A	ENSP00000359428.2	Q13495-1
	MAMLD1	ENST00000426613.5	TSL:1	c.97-2716A>G		intron	N/A	ENSP00000397438.2	Q13495-4
	MAMLD1	ENST00000682016.1		c.172-2716A>G		intron	N/A	ENSP00000507991.1	A0A804HKM8

Frequencies

GnomAD3 genomes AF: 0.111 AC: 9571 AN: 86379 Hom.: 460 Cov.: 17

Gnomad AFR AF: 0.0546

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0833

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0779

Gnomad SAS AF: 0.0911

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.111 AC: 9567 AN: 86392 Hom.: 461 Cov.: 17 AF XY: 0.107 AC XY: 2112 AN XY: 19822

African (AFR) AF: 0.0546 AC: 1139 AN: 20854

American (AMR) AF: 0.0832 AC: 468 AN: 5622

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 333 AN: 2451

East Asian (EAS) AF: 0.0777 AC: 210 AN: 2701

South Asian (SAS) AF: 0.0925 AC: 149 AN: 1611

European-Finnish (FIN) AF: 0.184 AC: 573 AN: 3112

Middle Eastern (MID) AF: 0.150 AC: 19 AN: 127

European-Non Finnish (NFE) AF: 0.135 AC: 6489 AN: 48224

Other (OTH) AF: 0.105 AC: 113 AN: 1076

Alfa AF: 0.117 Hom.: 5548

Bravo AF: 0.0865

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.47
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

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

Other links and lift over

dbSNP: rs17252936; hg19: chrX-149635295;