rs782263607

Variant names:

• chrX-150469979-A-G
• NM_005491.5:c.406A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-150469979-A-G
• chrX-150469979-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005491.5(MAMLD1):​c.406A>G​(p.Met136Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,239 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: MAMLD1 NM_005491.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.652

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14887863).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAMLD1	NM_005491.5	c.406A>G	p.Met136Val	missense_variant	Exon 4 of 8	ENST00000370401.7	NP_005482.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAMLD1	ENST00000370401.7	c.406A>G	p.Met136Val	missense_variant	Exon 4 of 8	5	NM_005491.5	ENSP00000359428.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098239 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 363593

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.60
DANN	Benign	0.36
DEOGEN2	Benign	0.060	T;.;T;.;T
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.75	.;T;T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.;.;.;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.5	N;N;D;N;N
REVEL	Benign	0.047
Sift	Benign	0.089	T;T;T;T;T
Sift4G	Benign	0.46	T;T;T;T;T
Polyphen		0.0010	B;B;.;B;B
Vest4		0.12
MutPred		0.21		Loss of disorder (P = 0.0724);.;Loss of disorder (P = 0.0724);.;Loss of disorder (P = 0.0724);
MVP		0.17
MPC		0.21
ClinPred		0.097	T
GERP RS		-1.4
Varity_R		0.25
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-149638251;