rs2179575

Variant names:

• chrX-150425249-G-C
• rs2179575
• NM_005491.5:c.-63-20205G>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MAMLD1	NM_005491.5	c.-63-20205G>C		intron_variant	Intron 1 of 7	ENST00000370401.7	NP_005482.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAMLD1	ENST00000370401.7	c.-63-20205G>C		intron_variant	Intron 1 of 7	5	NM_005491.5	ENSP00000359428.2

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 7967 AN: 110627 Hom.: 381 Cov.: 23

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

African (AFR) AF: 0.167 AC: 5072 AN: 30386

American (AMR) AF: 0.0649 AC: 675 AN: 10398

Ashkenazi Jewish (ASJ) AF: 0.0327 AC: 86 AN: 2631

East Asian (EAS) AF: 0.105 AC: 364 AN: 3481

South Asian (SAS) AF: 0.0762 AC: 199 AN: 2610

European-Finnish (FIN) AF: 0.0213 AC: 125 AN: 5876

Middle Eastern (MID) AF: 0.0138 AC: 3 AN: 217

European-Non Finnish (NFE) AF: 0.0257 AC: 1359 AN: 52887

Other (OTH) AF: 0.0647 AC: 98 AN: 1514

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
PhyloP100		0.34

Splicing

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

Other links and lift over

dbSNP: rs2179575; hg19: chrX-149593525;