rs3816605

Positions:

• chr11-47835701-T-A
• chr11-47835701-T-C
• chr11-47835701-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015231.3(NUP160):​c.949A>T​(p.Thr317Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T317A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NUP160 NM_015231.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.707

Genes affected

NUP160 (HGNC:18017): (nucleoporin 160) A structural constituent of nuclear pore. Involved in mRNA export from nucleus and nephron development. Part of nuclear pore outer ring. Colocalizes with kinetochore. Implicated in nephrotic syndrome type 19. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03942424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP160	NM_015231.3	c.949A>T	p.Thr317Ser	missense_variant	7/36	ENST00000378460.7
NUP160	NR_134636.3	n.981A>T		non_coding_transcript_exon_variant	7/36

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP160	ENST00000378460.7	c.949A>T	p.Thr317Ser	missense_variant	7/36	1	NM_015231.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450984 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 721218

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.8
DANN	Benign	0.30
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.51	D
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.88	N
MutationTaster	Benign	0.99	P;P;P;P
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.027
Sift	Benign	1.0	T
Sift4G	Benign	0.97	T
Polyphen		0.0	B
Vest4		0.088
MutPred		0.22		Loss of sheet (P = 0.0817);
MVP		0.16
MPC		0.18
ClinPred		0.024	T
GERP RS		0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.021
gMVP		0.068

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: rs3816605; hg19: chr11-47857253;