rs41313406

chrX-150470648-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005491.5(MAMLD1):c.1075C>T(p.Pro359Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,209,970 control chromosomes in the GnomAD database, including 5,619 homozygotes. There are 42,894 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.082 (408 hom., 2550 hem., cov: 23)
  • Exomes 𝑓: 0.11 (5211 hom. 40344 hem.)
• Consequence: MAMLD1 NM_005491.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.09

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017882288).
• BP6: Variant X-150470648-C-T is Benign according to our data. Variant chrX-150470648-C-T is described in ClinVar as [Benign]. Clinvar id is 1542510.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAMLD1	NM_005491.5	c.1075C>T	p.Pro359Ser	missense_variant	4/8	ENST00000370401.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAMLD1	ENST00000370401.7	c.1075C>T	p.Pro359Ser	missense_variant	4/8	5	NM_005491.5	A2

Frequencies

GnomAD3 genomes AF: 0.0825 AC: 9227 AN: 111791 Hom.: 408 Cov.: 23 AF XY: 0.0751 AC XY: 2550 AN XY: 33969

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0765

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.000280

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.106

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.0885

GnomAD3 exomes AF: 0.0829 AC: 15030 AN: 181336 Hom.: 506 AF XY: 0.0851 AC XY: 5691 AN XY: 66858

Gnomad AFR exome AF: 0.0136

Gnomad AMR exome AF: 0.0476

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.000289

Gnomad SAS exome AF: 0.0320

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.121

Gnomad OTH exome AF: 0.0967

GnomAD4 exome AF: 0.113 AC: 123680 AN: 1098127 Hom.: 5211 Cov.: 35 AF XY: 0.111 AC XY: 40344 AN XY: 363487

Gnomad4 AFR exome AF: 0.0147

Gnomad4 AMR exome AF: 0.0519

Gnomad4 ASJ exome AF: 0.135

Gnomad4 EAS exome AF: 0.000232

Gnomad4 SAS exome AF: 0.0354

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.0825 AC: 9222 AN: 111843 Hom.: 408 Cov.: 23 AF XY: 0.0749 AC XY: 2550 AN XY: 34031

Gnomad4 AFR AF: 0.0149

Gnomad4 AMR AF: 0.0763

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.000281

Gnomad4 SAS AF: 0.0210

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.0861

Alfa AF: 0.119 Hom.: 5264

Bravo AF: 0.0788

ESP6500AA AF: 0.0177 AC: 68

ESP6500EA AF: 0.126 AC: 846

ExAC AF: 0.0841 AC: 10215

EpiCase AF: 0.125

EpiControl AF: 0.123

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	11
Dann	Uncertain	0.98
DEOGEN2	Benign	0.049	T;.;.;T
FATHMM_MKL	Benign	0.14	N
MetaRNN	Benign	0.0018	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	2.0	M;.;.;M
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Benign	0.44	T;T;T;T
Polyphen		0.78	P;B;D;P
Vest4		0.083
MPC		0.35
ClinPred		0.023	T
GERP RS		0.28
Varity_R		0.14
gMVP		0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs41313406; hg19: chrX-149638920; COSMIC: COSV53375005; COSMIC: COSV53375005;