rs2073043

chrX-150473747-A-G

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.1985A>G(p.Asn662Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,202,243 control chromosomes in the GnomAD database, including 7,994 homozygotes. There are 51,547 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/16 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 0.10 (583 hom., 3233 hem., cov: 23)
  • Exomes 𝑓: 0.14 (7411 hom. 48314 hem.)
• Consequence: MAMLD1 NM_005491.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.441

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=0.0011407137).
• BP6: Variant X-150473747-A-G is Benign according to our data. Variant chrX-150473747-A-G is described in ClinVar as [Benign]. Clinvar id is 1598681.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAMLD1	NM_005491.5	c.1985A>G	p.Asn662Ser	missense_variant	5/8	ENST00000370401.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAMLD1	ENST00000370401.7	c.1985A>G	p.Asn662Ser	missense_variant	5/8	5	NM_005491.5	A2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 11515 AN: 110226 Hom.: 581 Cov.: 23 AF XY: 0.0988 AC XY: 3231 AN XY: 32696

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0517

Gnomad SAS AF: 0.0400

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.106

GnomAD3 exomes AF: 0.110 AC: 20147 AN: 183205 Hom.: 799 AF XY: 0.112 AC XY: 7549 AN XY: 67671

Gnomad AFR exome AF: 0.0233

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.0573

Gnomad SAS exome AF: 0.0491

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.142

Gnomad OTH exome AF: 0.117

GnomAD4 exome AF: 0.136 AC: 148987 AN: 1091963 Hom.: 7411 Cov.: 30 AF XY: 0.135 AC XY: 48314 AN XY: 357593

Gnomad4 AFR exome AF: 0.0244

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.159

Gnomad4 EAS exome AF: 0.0541

Gnomad4 SAS exome AF: 0.0527

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.104 AC: 11515 AN: 110280 Hom.: 583 Cov.: 23 AF XY: 0.0987 AC XY: 3233 AN XY: 32760

Gnomad4 AFR AF: 0.0263

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.0519

Gnomad4 SAS AF: 0.0405

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.104

Alfa AF: 0.126 Hom.: 2901

Bravo AF: 0.102

TwinsUK AF: 0.148 AC: 549

ALSPAC AF: 0.144 AC: 417

ESP6500AA AF: 0.0300 AC: 115

ESP6500EA AF: 0.145 AC: 976

ExAC AF: 0.110 AC: 13328

EpiCase AF: 0.144

EpiControl AF: 0.142

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	0.096
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	9.3
Dann	Benign	0.94
DEOGEN2	Benign	0.040	T;.;T
FATHMM_MKL	Benign	0.031	N
MetaRNN	Benign	0.0011	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;L
MutationTaster	Benign	1.0	P;P;P;P;P
PROVEAN	Benign	-0.45	N;N;N
REVEL	Benign	0.032
Sift	Benign	0.039	D;D;D
Sift4G	Benign	0.65	T;T;T
Polyphen		0.34	B;B;B
Vest4		0.025
ClinPred		0.0038	T
GERP RS		2.5
Varity_R		0.053

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: rs2073043; hg19: chrX-149642019; COSMIC: COSV53375035; COSMIC: COSV53375035;