Genetic Variant MXRA7:p.Asp135Asp (chr17-76688114-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_198530.4(MXRA7):c.405C>T(p.Asp135Asp) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000363 in 1,611,144 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 1 hom. )

Consequence

MXRA7
NM_198530.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0002383

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.83

Publications

2 publications found

Variant links:

Genes affected

MXRA7 (HGNC:7541): (matrix remodeling associated 7) Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

MXRA7 links:

SNHG16 (HGNC:44352): (small nucleolar RNA host gene 16)

SNHG16 links:

ENSG00000296346 (HGNC:):

ENSG00000296346 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP7

Synonymous conserved (PhyloP=-1.83 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198530.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MXRA7	NM_198530.4	MANE Select	c.405C>T	p.Asp135Asp	splice_region synonymous	Exon 2 of 4	NP_940932.2
MXRA7	NM_001387276.1		c.534C>T	p.Asp178Asp	splice_region synonymous	Exon 1 of 3	NP_001374205.1
MXRA7	NM_001387277.1		c.534C>T	p.Asp178Asp	splice_region synonymous	Exon 1 of 4	NP_001374206.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MXRA7	ENST00000449428.7	TSL:1 MANE Select	c.405C>T	p.Asp135Asp	splice_region synonymous	Exon 2 of 4	ENSP00000391466.1	P84157-2
MXRA7	ENST00000592148.1	TSL:1	c.534C>T	p.Asp178Asp	splice_region synonymous	Exon 1 of 3	ENSP00000465103.1	Q6ZR64
MXRA7	ENST00000589082.1	TSL:4	c.-61C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	ENSP00000467510.1	K7EPS4

Frequencies

GnomAD3 genomes

AF:

0.000198

AC:

AN:

151578

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000955

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000323

AC:

AN:

251022

AF XY:

0.000391

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.000894

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000450

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000380

AC:

555

AN:

1459448

Hom.:

Cov.:

AF XY:

0.000365

AC XY:

265

AN XY:

725968

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33400

American (AMR)

AF:

0.000112

AC:

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.000882

AC:

AN:

26070

East Asian (EAS)

AF:

0.000101

AC:

AN:

39558

South Asian (SAS)

AF:

0.000278

AC:

AN:

86188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53288

Middle Eastern (MID)

AF:

0.00185

AC:

AN:

5400

European-Non Finnish (NFE)

AF:

0.000418

AC:

464

AN:

1110698

Other (OTH)

AF:

0.000399

AC:

AN:

60206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

121

151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000198

AC:

AN:

151696

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74124

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41370

American (AMR)

AF:

0.000197

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.000866

AC:

AN:

3466

East Asian (EAS)

AF:

0.000196

AC:

AN:

5114

South Asian (SAS)

AF:

0.00

AC:

AN:

4784

European-Finnish (FIN)

AF:

0.0000955

AC:

AN:

10468

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

67928

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.000428

Hom.:

Bravo

AF:

0.000280

EpiCase

AF:

0.000763

EpiControl

AF:

0.000474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.014

(source)

DANN

Benign

0.33

PhyloP100

-1.8

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00024

dbscSNV1_RF

Benign

0.034

SpliceAI score (max)

0.010

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