NM_005701.4:c.485G>A

Variant names:

• chr15-75609575-C-T
• rs779814386
• NM_005701.4:c.485G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005701.4(SNUPN):​c.485G>A​(p.Arg162Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,613,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: SNUPN NM_005701.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.189
• Publications: 3 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.082140476).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNUPN	NM_005701.4	MANE Select	c.485G>A	p.Arg162Gln	missense	Exon 5 of 9	NP_005692.1	O95149
	SNUPN	NM_001042581.2		c.485G>A	p.Arg162Gln	missense	Exon 5 of 9	NP_001036046.1	O95149
	SNUPN	NM_001042588.2		c.485G>A	p.Arg162Gln	missense	Exon 5 of 9	NP_001036053.1	O95149

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNUPN	ENST00000308588.10	TSL:1 MANE Select	c.485G>A	p.Arg162Gln	missense	Exon 5 of 9	ENSP00000309831.5	O95149
	SNUPN	ENST00000896168.1		c.485G>A	p.Arg162Gln	missense	Exon 5 of 9	ENSP00000566227.1
	SNUPN	ENST00000934023.1		c.485G>A	p.Arg162Gln	missense	Exon 5 of 9	ENSP00000604082.1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152160 Hom.: 0 Cov.: 31

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: 0.000118

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251456 AF XY: 0.0000294

Gnomad AFR exome AF: 0.0000615

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: 0.0000527

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000575 AC: 84 AN: 1461398 Hom.: 0 Cov.: 30 AF XY: 0.0000646 AC XY: 47 AN XY: 727028

African (AFR) AF: 0.0000598 AC: 2 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000657 AC: 73 AN: 1111560

Other (OTH) AF: 0.0000994 AC: 6 AN: 60380

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152160 Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68030

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.0000772 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.19
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.065
Sift	Benign	0.24	T
Sift4G	Benign	0.26	T
Polyphen		0.0020	B
Vest4		0.094
MVP		0.51
MPC		0.14
ClinPred		0.079	T
GERP RS		-2.7
Varity_R		0.12
gMVP		0.21
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs779814386; hg19: chr15-75901916; COSMIC: COSV57947975; COSMIC: COSV57947975;