Genetic Variant NM_005701.4:c.249T>C (chr15-75617462-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005701.4(SNUPN):c.249T>C(p.Asp83Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0966 in 1,613,498 control chromosomes in the GnomAD database, including 8,729 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.078 ( 618 hom., cov: 32)

Exomes 𝑓: 0.099 ( 8111 hom. )

Consequence

SNUPN
NM_005701.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40

Publications

15 publications found

Variant links:

Genes affected

SNUPN (HGNC:14245): (snurportin 1) The nuclear import of the spliceosomal snRNPs U1, U2, U4 and U5, is dependent on the presence of a complex nuclear localization signal. The latter is composed of the 5'-2,2,7-terminal trimethylguanosine (m3G) cap structure of the U snRNA and the Sm core domain. The protein encoded by this gene interacts specifically with m3G-cap and functions as an snRNP-specific nuclear import receptor. Alternatively spliced transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

SNUPN Gene-Disease associations (from GenCC):

muscular dystrophy, limb-girdle, autosomal recessive 29
Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics

SNUPN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP7

Synonymous conserved (PhyloP=-1.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNUPN	NM_005701.4 link	c.249T>C	p.Asp83Asp	synonymous_variant	Exon 3 of 9	ENST00000308588.10	NP_005692.1	O95149
SNUPN	NM_001042581.2 link	c.249T>C	p.Asp83Asp	synonymous_variant	Exon 3 of 9		NP_001036046.1	O95149
SNUPN	NM_001042588.2 link	c.249T>C	p.Asp83Asp	synonymous_variant	Exon 3 of 9		NP_001036053.1	O95149

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNUPN	ENST00000308588.10 link	c.249T>C	p.Asp83Asp	synonymous_variant	Exon 3 of 9	1	NM_005701.4	ENSP00000309831.5		O95149

Frequencies

GnomAD3 genomes

AF:

0.0779

AC:

11828

AN:

151792

Hom.:

616

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0329

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.0563

Gnomad MID

AF:

0.125

Gnomad NFE

AF:

0.0962

Gnomad OTH

AF:

0.0966

GnomAD2 exomes

AF:

0.0943

AC:

23702

AN:

251270

AF XY:

0.101

show subpopulations

Gnomad AFR exome

AF:

0.0304

Gnomad AMR exome

AF:

0.0962

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.000598

Gnomad FIN exome

AF:

0.0578

Gnomad NFE exome

AF:

0.0955

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.0985

AC:

144001

AN:

1461588

Hom.:

8111

Cov.:

AF XY:

0.102

AC XY:

73858

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.0328

AC:

1099

AN:

33472

American (AMR)

AF:

0.0964

AC:

4306

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

3203

AN:

26124

East Asian (EAS)

AF:

0.000655

AC:

AN:

39690

South Asian (SAS)

AF:

0.192

AC:

16575

AN:

86220

European-Finnish (FIN)

AF:

0.0592

AC:

3164

AN:

53420

Middle Eastern (MID)

AF:

0.201

AC:

1157

AN:

5764

European-Non Finnish (NFE)

AF:

0.0974

AC:

108308

AN:

1111832

Other (OTH)

AF:

0.102

AC:

6163

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

6235

12471

18706

24942

31177

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4030

8060

12090

16120

20150

<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:

0.0779

AC:

11832

AN:

151910

Hom.:

618

Cov.:

AF XY:

0.0792

AC XY:

5881

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.0329

AC:

1362

AN:

41394

American (AMR)

AF:

0.100

AC:

1525

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

411

AN:

3468

East Asian (EAS)

AF:

0.00174

AC:

AN:

5176

South Asian (SAS)

AF:

0.195

AC:

938

AN:

4812

European-Finnish (FIN)

AF:

0.0563

AC:

592

AN:

10520

Middle Eastern (MID)

AF:

0.117

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0962

AC:

6541

AN:

67976

Other (OTH)

AF:

0.0960

AC:

203

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

531

1061

1592

2122

2653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<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:

0.0904

Hom.:

581

Bravo

AF:

0.0765

Asia WGS

AF:

0.0730

AC:

254

AN:

3478

EpiCase

AF:

0.106

EpiControl

AF:

0.106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.8

(source)

DANN

Benign

0.54

PhyloP100

-1.4

PromoterAI

0.048

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=90/10

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over