11-47835701-T-G

Position:

• 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>C​(p.Thr317Pro) 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 1,450,670 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=0.007954776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP160	NM_015231.3	c.949A>C	p.Thr317Pro	missense_variant	7/36	ENST00000378460.7
NUP160	NR_134636.3	n.981A>C		non_coding_transcript_exon_variant	7/36

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP160	ENST00000378460.7	c.949A>C	p.Thr317Pro	missense_variant	7/36	1	NM_015231.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000413 AC: 1 AN: 241994 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 130834

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000470

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450670 Hom.: 0 Cov.: 35 AF XY: 0.00000139 AC XY: 1 AN XY: 721062

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

ExAC AF: 0.00168 AC: 204

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.71
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.0080	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	0.88	P;P;P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.058
Sift	Benign	0.045	D
Sift4G	Uncertain	0.013	D
Polyphen		0.070	B
Vest4		0.25
MutPred		0.40		Gain of catalytic residue at P350 (P = 0.0126);
MVP		0.31
MPC		0.55
ClinPred		0.19	T
GERP RS		0.28
Varity_R		0.22
gMVP		0.34

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;