NM_138702.1:c.683A>G

Variant names:

• chrX-141881570-A-G
• rs145822629
• NM_138702.1:c.683A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_138702.1(MAGEC3):​c.683A>G​(p.Lys228Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,209,433 control chromosomes in the GnomAD database, including 20 homozygotes. There are 437 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (7 hom., 177 hem., cov: 23)
  • Exomes 𝑓: 0.00089 (13 hom. 260 hem.)
• Consequence: MAGEC3 NM_138702.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0290
• Publications: 2 publications found

Genes affected

MAGEC3 (HGNC:23798): (MAGE family member C3) This gene is a member of the MAGEC gene family. The members of this family are not expressed in normal tissues, except for testis, and are expressed in tumors of various histological types. The MAGEC genes are clustered on chromosome Xq26-q27. Two transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006769985).
• BP6: Variant X-141881570-A-G is Benign according to our data. Variant chrX-141881570-A-G is described in ClinVar as Benign. ClinVar VariationId is 789873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00605 (677/111857) while in subpopulation AFR AF = 0.0196 (603/30773). AF 95% confidence interval is 0.0183. There are 7 homozygotes in GnomAd4. There are 177 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138702.1. 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
	MAGEC3	NM_138702.1	MANE Select	c.683A>G	p.Lys228Arg	missense	Exon 4 of 8	NP_619647.1	Q8TD91-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEC3	ENST00000298296.1	TSL:1 MANE Select	c.683A>G	p.Lys228Arg	missense	Exon 4 of 8	ENSP00000298296.1	Q8TD91-1
	MAGEC3	ENST00000409007.2	TSL:1	c.-477+706A>G		intron	N/A	ENSP00000386566.1
	MAGEC3	ENST00000443323.2	TSL:1	c.-119+967A>G		intron	N/A	ENSP00000438254.1	Q3SYA6

Frequencies

GnomAD3 genomes AF: 0.00604 AC: 675 AN: 111809 Hom.: 7 Cov.: 23

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.000188

Gnomad OTH AF: 0.00403

GnomAD2 exomes AF: 0.00175 AC: 319 AN: 182788 AF XY: 0.00114

Gnomad AFR exome AF: 0.0205

Gnomad AMR exome AF: 0.000768

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000233

Gnomad OTH exome AF: 0.00222

GnomAD4 exome AF: 0.000889 AC: 976 AN: 1097576 Hom.: 13 Cov.: 31 AF XY: 0.000716 AC XY: 260 AN XY: 362942

African (AFR) AF: 0.0229 AC: 604 AN: 26357

American (AMR) AF: 0.00165 AC: 58 AN: 35147

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19357

East Asian (EAS) AF: 0.00 AC: 0 AN: 30196

South Asian (SAS) AF: 0.0000925 AC: 5 AN: 54074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40524

Middle Eastern (MID) AF: 0.00339 AC: 14 AN: 4130

European-Non Finnish (NFE) AF: 0.000201 AC: 169 AN: 841723

Other (OTH) AF: 0.00274 AC: 126 AN: 46068

GnomAD4 genome AF: 0.00605 AC: 677 AN: 111857 Hom.: 7 Cov.: 23 AF XY: 0.00520 AC XY: 177 AN XY: 34047

African (AFR) AF: 0.0196 AC: 603 AN: 30773

American (AMR) AF: 0.00537 AC: 57 AN: 10623

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3520

South Asian (SAS) AF: 0.00 AC: 0 AN: 2647

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6094

Middle Eastern (MID) AF: 0.00461 AC: 1 AN: 217

European-Non Finnish (NFE) AF: 0.000188 AC: 10 AN: 53147

Other (OTH) AF: 0.00398 AC: 6 AN: 1508

Alfa AF: 0.00265 Hom.: 115

Bravo AF: 0.00797

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000692 AC: 2

ESP6500AA AF: 0.0172 AC: 66

ESP6500EA AF: 0.000297 AC: 2

ExAC AF: 0.00199 AC: 242

EpiCase AF: 0.0000545

EpiControl AF: 0.000475

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.92	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	5.9
DANN	Benign	0.90
DEOGEN2	Benign	0.013	T
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0068	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.85	L
PhyloP100		-0.029
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.049
Sift	Benign	0.49	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.017	B
Vest4		0.11
MVP		0.10
MPC		0.076
ClinPred		0.00032	T
GERP RS		-1.8
Varity_R		0.040
gMVP		0.22
Mutation Taster		=99/1	polymorphism (auto)

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: rs145822629; hg19: chrX-140969356;