X-152736410-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001166387.4(MAGEA12):c.249C>T(p.Ser83=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,209,590 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000063 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000048 (0 hom. 24 hem.)
• Consequence: MAGEA12 NM_001166387.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.23

Genes affected

MAGEA12 (HGNC:6799): (MAGE family member A12) This gene is closely related to several other genes clustered on chromosome X. These genes may be overexpressed in tumors. Multiple alternatively spliced variants encoding the same protein have been identified. [provided by RefSeq, Jun 2014]

CSAG4 (HGNC:20923): (CSAG family member 4 (pseudogene))

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant X-152736410-C-T is Benign according to our data. Variant chrX-152736410-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661672.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.23 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGEA12	NM_001166387.4	c.249C>T	p.Ser83=	synonymous_variant	3/3	ENST00000393869.8
CSAG4	NR_073432.1	n.33+2551C>T		intron_variant, non_coding_transcript_variant
MAGEA12	NM_001166386.3	c.249C>T	p.Ser83=	synonymous_variant	3/3
MAGEA12	NM_005367.7	c.249C>T	p.Ser83=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGEA12	ENST00000393869.8	c.249C>T	p.Ser83=	synonymous_variant	3/3	2	NM_001166387.4	P1
MAGEA12	ENST00000357916.8	c.249C>T	p.Ser83=	synonymous_variant	2/2	1		P1
MAGEA12	ENST00000393900.4	c.249C>T	p.Ser83=	synonymous_variant	3/3	1		P1
CSAG4	ENST00000361201.8	n.33+2551C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000627 AC: 7 AN: 111647 Hom.: 0 Cov.: 23 AF XY: 0.0000296 AC XY: 1 AN XY: 33831

Gnomad AFR AF: 0.0000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000944

Gnomad ASJ AF: 0.00113

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000983 AC: 18 AN: 183138 Hom.: 0 AF XY: 0.0000592 AC XY: 4 AN XY: 67594

Gnomad AFR exome AF: 0.000152

Gnomad AMR exome AF: 0.000438

Gnomad ASJ exome AF: 0.000268

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000443

GnomAD4 exome AF: 0.0000483 AC: 53 AN: 1097943 Hom.: 0 Cov.: 31 AF XY: 0.0000661 AC XY: 24 AN XY: 363299

Gnomad4 AFR exome AF: 0.000227

Gnomad4 AMR exome AF: 0.000426

Gnomad4 ASJ exome AF: 0.000361

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000370

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000261

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000627 AC: 7 AN: 111647 Hom.: 0 Cov.: 23 AF XY: 0.0000296 AC XY: 1 AN XY: 33831

Gnomad4 AFR AF: 0.0000652

Gnomad4 AMR AF: 0.0000944

Gnomad4 ASJ AF: 0.00113

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000174 Hom.: 2

Bravo AF: 0.000125

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

MAGEA12: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.2
Dann	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1556833388; hg19: chrX-151900552;