15-75617462-A-G

Position:

• chr15-75617462-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SNUPN	NM_005701.4	c.249T>C	p.Asp83Asp	synonymous_variant	3/9	ENST00000308588.10	NP_005692.1
SNUPN	NM_001042581.2	c.249T>C	p.Asp83Asp	synonymous_variant	3/9		NP_001036046.1
SNUPN	NM_001042588.2	c.249T>C	p.Asp83Asp	synonymous_variant	3/9		NP_001036053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNUPN	ENST00000308588.10	c.249T>C	p.Asp83Asp	synonymous_variant	3/9	1	NM_005701.4	ENSP00000309831.5

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

GnomAD3 exomes AF: 0.0943 AC: 23702 AN: 251270 Hom.: 1498 AF XY: 0.101 AC XY: 13750 AN XY: 135804

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 SAS exome AF: 0.192

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

Gnomad4 AFR exome AF: 0.0328

Gnomad4 AMR exome AF: 0.0964

Gnomad4 ASJ exome AF: 0.123

Gnomad4 EAS exome AF: 0.000655

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.0592

Gnomad4 NFE exome AF: 0.0974

Gnomad4 OTH exome AF: 0.102

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

Gnomad4 AFR AF: 0.0329

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.0563

Gnomad4 NFE AF: 0.0962

Gnomad4 OTH AF: 0.0960

Alfa AF: 0.0900 Hom.: 531

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
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs11547316; hg19: chr15-75909803;