1-154022171-C-T

Variant names:

• chr1-154022171-C-T
• rs11264875
• ENST00000368559.8:c.4471G>A

Variant summary

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

The ENST00000368559.8(NUP210L):​c.4471G>A​(p.Val1491Ile) variant causes a missense change. The variant allele was found at a frequency of 0.29 in 1,613,150 control chromosomes in the GnomAD database, including 69,763 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 0.27 (5790 hom., cov: 31)
  • Exomes 𝑓: 0.29 (63973 hom.)
• Consequence: NUP210L ENST00000368559.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.25
• Publications: 38 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 (MetaRNN=0.0064232945).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP210L	NM_207308.3	c.4471G>A	p.Val1491Ile	missense_variant	Exon 32 of 40		NP_997191.2
NUP210L	NM_001159484.1	c.4471G>A	p.Val1491Ile	missense_variant	Exon 32 of 38		NP_001152956.1
NUP210L	XM_017002788.3	c.4471G>A	p.Val1491Ile	missense_variant	Exon 32 of 39		XP_016858277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP210L	ENST00000368559.8	c.4471G>A	p.Val1491Ile	missense_variant	Exon 32 of 40	5		ENSP00000357547.3
NUP210L	ENST00000368553.5	c.1270G>A	p.Val424Ile	missense_variant	Exon 10 of 16	1		ENSP00000357541.1
NUP210L	ENST00000271854.3	c.4471G>A	p.Val1491Ile	missense_variant	Exon 32 of 38	5		ENSP00000271854.3

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40581 AN: 151738 Hom.: 5782 Cov.: 31

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.288

GnomAD2 exomes AF: 0.313 AC: 77990 AN: 249556 AF XY: 0.313

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.427

Gnomad ASJ exome AF: 0.305

Gnomad EAS exome AF: 0.267

Gnomad FIN exome AF: 0.332

Gnomad NFE exome AF: 0.298

Gnomad OTH exome AF: 0.327

GnomAD4 exome AF: 0.293 AC: 427766 AN: 1461294 Hom.: 63973 Cov.: 36 AF XY: 0.295 AC XY: 214230 AN XY: 726988

African (AFR) AF: 0.163 AC: 5445 AN: 33480

American (AMR) AF: 0.420 AC: 18805 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 7764 AN: 26134

East Asian (EAS) AF: 0.300 AC: 11907 AN: 39698

South Asian (SAS) AF: 0.320 AC: 27582 AN: 86242

European-Finnish (FIN) AF: 0.337 AC: 18006 AN: 53420

Middle Eastern (MID) AF: 0.322 AC: 1856 AN: 5768

European-Non Finnish (NFE) AF: 0.287 AC: 319369 AN: 1111462

Other (OTH) AF: 0.282 AC: 17032 AN: 60366

GnomAD4 genome AF: 0.267 AC: 40620 AN: 151856 Hom.: 5790 Cov.: 31 AF XY: 0.273 AC XY: 20235 AN XY: 74164

African (AFR) AF: 0.167 AC: 6915 AN: 41424

American (AMR) AF: 0.373 AC: 5673 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1008 AN: 3468

East Asian (EAS) AF: 0.283 AC: 1464 AN: 5172

South Asian (SAS) AF: 0.325 AC: 1563 AN: 4814

European-Finnish (FIN) AF: 0.336 AC: 3533 AN: 10500

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19563 AN: 67954

Other (OTH) AF: 0.286 AC: 603 AN: 2110

Alfa AF: 0.285 Hom.: 31701

Bravo AF: 0.268

TwinsUK AF: 0.297 AC: 1100

ALSPAC AF: 0.279 AC: 1076

ESP6500AA AF: 0.161 AC: 655

ESP6500EA AF: 0.274 AC: 2291

ExAC AF: 0.308 AC: 37211

Asia WGS AF: 0.283 AC: 984 AN: 3478

EpiCase AF: 0.297

EpiControl AF: 0.305

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.72	T;T;T
MetaRNN	Benign	0.0064	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;.;M
PhyloP100		4.2
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.62	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.054	T;T;T
Sift4G	Uncertain	0.014	D;D;D
Polyphen		0.98	D;.;.
Vest4		0.24
MPC		0.53
ClinPred		0.021	T
GERP RS		6.1
Varity_R		0.10
gMVP		0.66
Mutation Taster		=86/14	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: rs11264875; hg19: chr1-153994647; COSMIC: COSV55145512;