Genetic Variant NM_014061.5:c.204C>T (chrX-55452578-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014061.5(MAGEH1):c.204C>T(p.Ala68Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000828 in 1,208,407 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 0.000036 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000055 ( 0 hom. 2 hem. )

Consequence

MAGEH1
NM_014061.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.223

Publications

0 publications found

Variant links:

Genes affected

MAGEH1 (HGNC:24092): (MAGE family member H1) This gene belongs to the non-CT (non cancer/testis) subgroup of the melanoma-associated antigen (MAGE) superfamily. The encoded protein is likely associated with apoptosis, cell cycle arrest, growth inhibition or cell differentiation. The protein may be involved in the atRA (all-trans retinoic acid) signaling through the STAT1-alpha (signal transducer and activator of transcription 1-alpha) pathway. [provided by RefSeq, Aug 2013]

MAGEH1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant X-55452578-C-T is Benign according to our data. Variant chrX-55452578-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2660696.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.223 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014061.5. 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
	MAGEH1	NM_014061.5	MANE Select	c.204C>T	p.Ala68Ala	synonymous	Exon 1 of 1	NP_054780.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEH1	ENST00000342972.3	TSL:6 MANE Select	c.204C>T	p.Ala68Ala	synonymous	Exon 1 of 1	ENSP00000343706.1	Q9H213

Frequencies

GnomAD3 genomes

AF:

0.0000361

AC:

AN:

110927

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000952

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000567

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000552

AC:

AN:

181205

AF XY:

0.0000152

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1097480

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

362920

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26349

American (AMR)

AF:

0.00

AC:

AN:

35112

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19336

East Asian (EAS)

AF:

0.00

AC:

AN:

30201

South Asian (SAS)

AF:

0.00

AC:

AN:

53983

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40491

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.00000475

AC:

AN:

841818

Other (OTH)

AF:

0.0000217

AC:

AN:

46060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000361

AC:

AN:

110927

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33107

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30430

American (AMR)

AF:

0.0000952

AC:

AN:

10500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.00

AC:

AN:

3518

South Asian (SAS)

AF:

0.00

AC:

AN:

2565

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5957

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000567

AC:

AN:

52919

Other (OTH)

AF:

0.00

AC:

AN:

1477

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

-0.22

PromoterAI

0.046

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over