rs147340353

Variant names:

• chr6-17625935-G-A
• rs147340353
• NM_005124.4:c.3774C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-17625935-G-A
• chr6-17625935-G-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_005124.4(NUP153):​c.3774C>T​(p.Ser1258Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: NUP153 NM_005124.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.55

Genes affected

NUP153 (HGNC:8062): (nucleoporin 153) Nuclear pore complexes regulate the transport of macromolecules between the nucleus and cytoplasm. They are composed of at least 100 different polypeptide subunits, many of which belong to the nucleoporin family. Nucleoporins are glycoproteins found in nuclear pores and contain characteristic pentapeptide XFXFG repeats as well as O-linked N-acetylglucosamine residues oriented towards the cytoplasm. The protein encoded by this gene has three distinct domains: a N-terminal region containing a pore targeting and an RNA-binding domain domain, a central region containing multiple zinc finger motifs, and a C-terminal region containing multiple XFXFG repeats. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=2.55 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP153	NM_005124.4	c.3774C>T	p.Ser1258Ser	synonymous_variant	Exon 19 of 22	ENST00000262077.3	NP_005115.2
NUP153	NM_001278209.2	c.3867C>T	p.Ser1289Ser	synonymous_variant	Exon 20 of 23		NP_001265138.1
NUP153	NM_001278210.2	c.3648C>T	p.Ser1216Ser	synonymous_variant	Exon 18 of 21		NP_001265139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP153	ENST00000262077.3	c.3774C>T	p.Ser1258Ser	synonymous_variant	Exon 19 of 22	1	NM_005124.4	ENSP00000262077.3
NUP153	ENST00000613258.4	c.3648C>T	p.Ser1216Ser	synonymous_variant	Exon 18 of 21	1		ENSP00000478627.1
NUP153	ENST00000537253.5	c.3867C>T	p.Ser1289Ser	synonymous_variant	Exon 20 of 23	2		ENSP00000444029.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	8.4
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs147340353; hg19: chr6-17626166;