15-75617462-A-G

Variant names:

• chr15-75617462-A-G
• rs11547316
• NM_005701.4:c.249T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 15 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: 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.

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.249T>C	p.Asp83Asp	synonymous	Exon 3 of 9	NP_005692.1	O95149
	SNUPN	NM_001042581.2		c.249T>C	p.Asp83Asp	synonymous	Exon 3 of 9	NP_001036046.1	O95149
	SNUPN	NM_001042588.2		c.249T>C	p.Asp83Asp	synonymous	Exon 3 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.249T>C	p.Asp83Asp	synonymous	Exon 3 of 9	ENSP00000309831.5	O95149
	SNUPN	ENST00000896168.1		c.249T>C	p.Asp83Asp	synonymous	Exon 3 of 9	ENSP00000566227.1
	SNUPN	ENST00000934023.1		c.249T>C	p.Asp83Asp	synonymous	Exon 3 of 9	ENSP00000604082.1

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 11828 AN: 151792 Hom.: 616 Cov.: 32

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

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.: 32 AF XY: 0.102 AC XY: 73858 AN XY: 727116

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: 26 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

GnomAD4 genome AF: 0.0779 AC: 11832 AN: 151910 Hom.: 618 Cov.: 32 AF XY: 0.0792 AC XY: 5881 AN XY: 74232

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: 9 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: 34 AN: 290

European-Non Finnish (NFE) AF: 0.0962 AC: 6541 AN: 67976

Other (OTH) AF: 0.0960 AC: 203 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	3.8
DANN	Benign	0.54
PhyloP100		-1.4
PromoterAI		0.048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=90/10	polymorphism (auto)

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: rs11547316; hg19: chr15-75909803;