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GeneBe

X-150462831-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_005491.5(MAMLD1):c.156A>G(p.Pro52=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,206,952 control chromosomes in the GnomAD database, including 47 homozygotes. There are 825 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 17 hom., 370 hem., cov: 23)
Exomes 𝑓: 0.0016 ( 30 hom. 455 hem. )

Consequence

MAMLD1
NM_005491.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.138
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-150462831-A-G is Benign according to our data. Variant chrX-150462831-A-G is described in ClinVar as [Benign]. Clinvar id is 714971.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.138 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0129 (1450/112309) while in subpopulation AFR AF= 0.0439 (1354/30874). AF 95% confidence interval is 0.0419. There are 17 homozygotes in gnomad4. There are 370 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 17 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAMLD1NM_005491.5 linkuse as main transcriptc.156A>G p.Pro52= synonymous_variant 3/8 ENST00000370401.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAMLD1ENST00000370401.7 linkuse as main transcriptc.156A>G p.Pro52= synonymous_variant 3/85 NM_005491.5 A2Q13495-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0129
AC:
1453
AN:
112255
Hom.:
17
Cov.:
23
AF XY:
0.0108
AC XY:
371
AN XY:
34411
show subpopulations
Gnomad AFR
AF:
0.0441
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00563
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000326
Gnomad MID
AF:
0.00837
Gnomad NFE
AF:
0.000338
Gnomad OTH
AF:
0.00925
GnomAD3 exomes
AF:
0.00392
AC:
711
AN:
181375
Hom.:
18
AF XY:
0.00227
AC XY:
153
AN XY:
67257
show subpopulations
Gnomad AFR exome
AF:
0.0502
Gnomad AMR exome
AF:
0.00165
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000211
Gnomad FIN exome
AF:
0.000628
Gnomad NFE exome
AF:
0.000246
Gnomad OTH exome
AF:
0.00269
GnomAD4 exome
AF:
0.00156
AC:
1712
AN:
1094643
Hom.:
30
Cov.:
29
AF XY:
0.00126
AC XY:
455
AN XY:
360091
show subpopulations
Gnomad4 AFR exome
AF:
0.0485
Gnomad4 AMR exome
AF:
0.00236
Gnomad4 ASJ exome
AF:
0.0000517
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000241
Gnomad4 FIN exome
AF:
0.000815
Gnomad4 NFE exome
AF:
0.000184
Gnomad4 OTH exome
AF:
0.00311
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0129
AC:
1450
AN:
112309
Hom.:
17
Cov.:
23
AF XY:
0.0107
AC XY:
370
AN XY:
34475
show subpopulations
Gnomad4 AFR
AF:
0.0439
Gnomad4 AMR
AF:
0.00562
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000326
Gnomad4 NFE
AF:
0.000338
Gnomad4 OTH
AF:
0.00914
Alfa
AF:
0.00738
Hom.:
59
Bravo
AF:
0.0153
EpiCase
AF:
0.000273
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeNov 25, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
Cadd
Benign
2.3
Dann
Benign
0.33

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs16996606; hg19: chrX-149631097; API