rs4845597

Variant names:

• chr1-154116962-T-C
• rs4845597
• ENST00000368559.8:c.1620+763A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000368559.8(NUP210L):​c.1620+763A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,952 control chromosomes in the GnomAD database, including 8,221 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 0.31 (8221 hom., cov: 31)
• Consequence: NUP210L ENST00000368559.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 8 publications found

Genes affected

NUP210L (HGNC:29915): (nucleoporin 210 like) Predicted to act upstream of or within Sertoli cell development and spermatid development. Predicted to be integral component of membrane. Predicted to be part of nuclear pore. [provided by Alliance of Genome Resources, Apr 2022]

NUP210L Gene-Disease associations (from GenCC):

• spermatogenic failure

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP210L	NM_207308.3	c.1620+763A>G		intron_variant	Intron 12 of 39		NP_997191.2
NUP210L	NM_001159484.1	c.1620+763A>G		intron_variant	Intron 12 of 37		NP_001152956.1
NUP210L	XM_017002788.3	c.1620+763A>G		intron_variant	Intron 12 of 38		XP_016858277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP210L	ENST00000368559.8	c.1620+763A>G		intron_variant	Intron 12 of 39	5		ENSP00000357547.3
NUP210L	ENST00000271854.3	c.1620+763A>G		intron_variant	Intron 12 of 37	5		ENSP00000271854.3

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47772 AN: 151834 Hom.: 8211 Cov.: 31

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.349

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.315 AC: 47817 AN: 151952 Hom.: 8221 Cov.: 31 AF XY: 0.321 AC XY: 23864 AN XY: 74244

African (AFR) AF: 0.181 AC: 7517 AN: 41482

American (AMR) AF: 0.454 AC: 6910 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1420 AN: 3470

East Asian (EAS) AF: 0.431 AC: 2227 AN: 5170

South Asian (SAS) AF: 0.375 AC: 1806 AN: 4822

European-Finnish (FIN) AF: 0.374 AC: 3938 AN: 10518

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22901 AN: 67954

Other (OTH) AF: 0.345 AC: 727 AN: 2108

Alfa AF: 0.322 Hom.: 1377

Bravo AF: 0.319

Asia WGS AF: 0.394 AC: 1368 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.49
PhyloP100		-0.084
Mutation Taster		=100/0	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: rs4845597; hg19: chr1-154089438;