1-153994184-T-G

Variant names:

• chr1-153994184-T-G
• rs4845360
• ENST00000368559.8:c.5491+892A>C

Variant summary

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

The ENST00000368559.8(NUP210L):​c.5491+892A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,008 control chromosomes in the GnomAD database, including 24,067 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 0.55 (24067 hom., cov: 32)
• Consequence: NUP210L ENST00000368559.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239
• Publications: 13 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 (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP210L	NM_207308.3	c.5491+892A>C		intron_variant	Intron 38 of 39		NP_997191.2
NUP210L	NM_001159484.1	c.5035+892A>C		intron_variant	Intron 36 of 37		NP_001152956.1
NUP210L	XM_017002788.3	c.5387-1095A>C		intron_variant	Intron 37 of 38		XP_016858277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP210L	ENST00000368559.8	c.5491+892A>C		intron_variant	Intron 38 of 39	5		ENSP00000357547.3
NUP210L	ENST00000368553.5	c.1834+892A>C		intron_variant	Intron 14 of 15	1		ENSP00000357541.1
NUP210L	ENST00000271854.3	c.5035+892A>C		intron_variant	Intron 36 of 37	5		ENSP00000271854.3

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84072 AN: 151890 Hom.: 24032 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.554 AC: 84157 AN: 152008 Hom.: 24067 Cov.: 32 AF XY: 0.563 AC XY: 41802 AN XY: 74304

African (AFR) AF: 0.600 AC: 24862 AN: 41448

American (AMR) AF: 0.643 AC: 9828 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1413 AN: 3472

East Asian (EAS) AF: 0.948 AC: 4899 AN: 5166

South Asian (SAS) AF: 0.666 AC: 3213 AN: 4822

European-Finnish (FIN) AF: 0.559 AC: 5900 AN: 10550

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32278 AN: 67954

Other (OTH) AF: 0.541 AC: 1143 AN: 2112

Alfa AF: 0.500 Hom.: 11968

Bravo AF: 0.566

Asia WGS AF: 0.769 AC: 2671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.92
DANN	Benign	0.69
PhyloP100		-0.24
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: rs4845360; hg19: chr1-153966660;