chrX-150462856-A-T

Variant names:

• chrX-150462856-A-T
• NM_005491.5:c.171+10A>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_005491.5(MAMLD1):​c.171+10A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAMLD1 NM_005491.5 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.233
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant X-150462856-A-T is Benign according to our data. Variant chrX-150462856-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3041234.Status of the report is no_assertion_criteria_provided, 0 stars.

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.171+10A>T		intron	N/A	NP_005482.2	Q13495-1
	MAMLD1	NM_001400512.1		c.171+10A>T		intron	N/A	NP_001387441.1	A0A804HKM8
	MAMLD1	NM_001177465.3		c.97-6889A>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.171+10A>T		intron	N/A	ENSP00000359428.2	Q13495-1
	MAMLD1	ENST00000426613.5	TSL:1	c.97-6889A>T		intron	N/A	ENSP00000397438.2	Q13495-4
	MAMLD1	ENST00000682016.1		c.171+10A>T		intron	N/A	ENSP00000507991.1	A0A804HKM8

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1060848 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 329952

African (AFR) AF: 0.00 AC: 0 AN: 25691

American (AMR) AF: 0.00 AC: 0 AN: 35096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19136

East Asian (EAS) AF: 0.00 AC: 0 AN: 30070

South Asian (SAS) AF: 0.00 AC: 0 AN: 53058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3732

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 808818

Other (OTH) AF: 0.00 AC: 0 AN: 44829

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MAMLD1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.83
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chrX-149631122;