ENST00000375695.2:c.169G>C

Variant names:

• chrX-51894750-G-C
• rs145588024
• ENST00000375695.2:c.169G>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000375695.2(MAGED1):​c.169G>C​(p.Val57Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V57I) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000019 (1 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGED1 ENST00000375695.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662

Genes affected

MAGED1 (HGNC:6813): (MAGE family member D1) This gene is a member of the melanoma antigen gene (MAGE) family. Most of the genes of this family encode tumor specific antigens that are not expressed in normal adult tissues except testis. Although the protein encoded by this gene shares strong homology with members of the MAGE family, it is expressed in almost all normal adult tissues. This gene has been demonstrated to be involved in the p75 neurotrophin receptor mediated programmed cell death pathway. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03876534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGED1	NM_006986.4	c.46-303G>C		intron_variant	Intron 2 of 12	ENST00000326587.12	NP_008917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGED1	ENST00000326587.12	c.46-303G>C		intron_variant	Intron 2 of 12	1	NM_006986.4	ENSP00000325333.8

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD3 exomes AF: 0.0000152 AC: 2 AN: 131293 Hom.: 1 AF XY: 0.00 AC XY: 0 AN XY: 43023

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000205

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000192 AC: 2 AN: 1042688 Hom.: 1 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 336590

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: 0.0000449

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

ExAC AF: 0.0000166 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-1.2
CADD	Benign	2.1
DANN	Benign	0.34
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.021
Sift	Benign	0.37	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.098		Gain of disorder (P = 0.145);
MVP		0.12
MPC		0.076
ClinPred		0.020	T
GERP RS		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.090

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: rs145588024; hg19: chrX-51637846;