Genetic Variant SNUPN:p.Asp83Glu (chr15-75617462-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005701.4(SNUPN):c.249T>G(p.Asp83Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SNUPN
NM_005701.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40

Publications

0 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, STRONG Submitted by: PanelApp Australia, Ambry Genetics
SNUPN-related muscular dystrophy with or without multi-system involvement
Inheritance: AR Classification: STRONG Submitted by: ClinGen

SNUPN links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037935406).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005701.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNUPN	NM_005701.4	MANE Select	c.249T>G	p.Asp83Glu	missense	Exon 3 of 9	NP_005692.1	O95149
SNUPN	NM_001042581.2		c.249T>G	p.Asp83Glu	missense	Exon 3 of 9	NP_001036046.1	O95149
SNUPN	NM_001042588.2		c.249T>G	p.Asp83Glu	missense	Exon 3 of 9	NP_001036053.1	O95149

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNUPN	ENST00000308588.10	TSL:1 MANE Select	c.249T>G	p.Asp83Glu	missense	Exon 3 of 9	ENSP00000309831.5	O95149
SNUPN	ENST00000896168.1		c.249T>G	p.Asp83Glu	missense	Exon 3 of 9	ENSP00000566227.1
SNUPN	ENST00000934023.1		c.249T>G	p.Asp83Glu	missense	Exon 3 of 9	ENSP00000604082.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111964

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.31

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.0030

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.53

M_CAP

Benign

0.00083

MetaRNN

Benign

0.038

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.50

PhyloP100

-1.4

PrimateAI

Benign

0.40

PROVEAN

Benign

0.32

REVEL

Benign

0.061

Sift

Benign

0.93

Sift4G

Benign

0.96

Polyphen

0.0010

Vest4

0.12

MVP

0.31

MPC

0.11

ClinPred

0.075

GERP RS

-6.4

PromoterAI

-0.0062

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.026

gMVP

0.13

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over