dbSNP rs185006165: MBNL3:c.772-5C>A (chrX-132386816-G-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001386889.1(MBNL3):c.772-5C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000207 in 1,204,860 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000037 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.000019 ( 0 hom. 8 hem. )

Consequence

MBNL3
NM_001386889.1 splice_region, intron

Scores

Splicing: ADA: 0.0001937

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.773

Publications

0 publications found

Variant links:

Genes affected

MBNL3 (HGNC:20564): (muscleblind like splicing regulator 3) This gene encodes a member of the muscleblind-like family of proteins. The encoded protein may function in regulation of alternative splicing and may play a role in the pathophysiology of myotonic dystrophy. Alternatively spliced transcript variants have been described. [provided by RefSeq, Dec 2009]

MBNL3 links:

RAP2C-AS1 (HGNC:40957): (RAP2C antisense RNA 1)

RAP2C-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant X-132386816-G-T is Benign according to our data. Variant chrX-132386816-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3043463.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAdExome4 at 8 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386889.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MBNL3	NM_001386889.1	MANE Select	c.772-5C>A	splice_region intron	N/A	NP_001373818.1	Q9NUK0-1
MBNL3	NM_001386891.1		c.772-5C>A	splice_region intron	N/A	NP_001373820.1
MBNL3	NM_001386892.1		c.772-5C>A	splice_region intron	N/A	NP_001373821.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MBNL3	ENST00000370853.8	TSL:1 MANE Select	c.772-5C>A	splice_region intron	N/A	ENSP00000359890.3	Q9NUK0-1
MBNL3	ENST00000370839.7	TSL:1	c.772-110C>A	intron	N/A	ENSP00000359876.3	Q9NUK0-2
MBNL3	ENST00000538204.6	TSL:1	c.622-5C>A	splice_region intron	N/A	ENSP00000439618.1	Q9NUK0-4

Frequencies

GnomAD3 genomes

AF:

0.0000367

AC:

AN:

108936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000189

Gnomad OTH

AF:

0.00202

GnomAD2 exomes

AF:

0.0000499

AC:

AN:

180358

AF XY:

0.0000753

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000367

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000723

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000373

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1095870

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

361484

show subpopulations

African (AFR)

AF:

0.0000380

AC:

AN:

26347

American (AMR)

AF:

0.0000284

AC:

AN:

35179

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19348

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30185

South Asian (SAS)

AF:

0.000148

AC:

AN:

53981

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40465

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3832

European-Non Finnish (NFE)

AF:

0.00000714

AC:

AN:

840542

Other (OTH)

AF:

0.0000870

AC:

AN:

45991

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000367

AC:

AN:

108990

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28313

American (AMR)

AF:

0.00

AC:

AN:

10447

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2639

East Asian (EAS)

AF:

0.00

AC:

AN:

3535

South Asian (SAS)

AF:

0.00

AC:

AN:

2632

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6004

Middle Eastern (MID)

AF:

0.00

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

53016

Other (OTH)

AF:

0.00199

AC:

AN:

1505

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

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:

0.000113

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MBNL3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.82

(source)

DANN

Benign

0.36

PhyloP100

0.77

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00019

dbscSNV1_RF

Benign

0.0080

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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