NM_002364.5:c.647A>C

Variant names:

• chrX-30219227-A-C
• rs149245405
• NM_002364.5:c.647A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002364.5(MAGEB2):​c.647A>C​(p.Asn216Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000897 in 111,502 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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. N216S) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 23)
• Consequence: MAGEB2 NM_002364.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28
• Publications: 1 publications found

Genes affected

MAGEB2 (HGNC:6809): (MAGE family member B2) This gene is a member of the MAGEB gene family. The members of this family have their entire coding sequences located in the last exon, and the encoded proteins show 50 to 68% sequence identity to each other. The promoters and first exons of the MAGEB genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. This gene is localized in the DSS (dosage-sensitive sex reversal) critical region. It is expressed in testis and placenta, and in a significant fraction of tumors of various histological types. The MAGEB genes are clustered on chromosome Xp22-p21. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002364.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEB2	NM_002364.5	MANE Select	c.647A>C	p.Asn216Thr	missense	Exon 2 of 2	NP_002355.2	O15479

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEB2	ENST00000378988.5	TSL:1 MANE Select	c.647A>C	p.Asn216Thr	missense	Exon 2 of 2	ENSP00000368273.4	O15479

Frequencies

GnomAD3 genomes AF: 0.00000897 AC: 1 AN: 111449 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000549 AC: 1 AN: 182177 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000725

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000897 AC: 1 AN: 111502 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33718

African (AFR) AF: 0.00 AC: 0 AN: 30693

American (AMR) AF: 0.00 AC: 0 AN: 10563

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.000282 AC: 1 AN: 3542

South Asian (SAS) AF: 0.00 AC: 0 AN: 2600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53017

Other (OTH) AF: 0.00 AC: 0 AN: 1515

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0033	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		2.3
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.084
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.99	D
Vest4		0.27
MutPred		0.81		Loss of helix (P = 0.2022)
MVP		0.26
MPC		0.0083
ClinPred		0.95	D
GERP RS		3.3
Varity_R		0.60
gMVP		0.38
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs149245405; hg19: chrX-30237344;