chr1-154022171-C-T

Position:

• chr1-154022171-C-T

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NUP210L	NM_207308.3	c.4471G>A	p.Val1491Ile	missense_variant	32/40	ENST00000368559.8
NUP210L	XM_011510122.2	c.4339G>A	p.Val1447Ile	missense_variant	31/39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP210L	ENST00000368559.8	c.4471G>A	p.Val1491Ile	missense_variant	32/40	5	NM_207308.3	P2
NUP210L	ENST00000368553.5	c.1270G>A	p.Val424Ile	missense_variant	10/16	1		A2
NUP210L	ENST00000271854.3	c.4471G>A	p.Val1491Ile	missense_variant	32/38	5		A2

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

GnomAD3 exomes AF: 0.313 AC: 77990 AN: 249556 Hom.: 12819 AF XY: 0.313 AC XY: 42370 AN XY: 135392

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 SAS exome AF: 0.324

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

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.420

Gnomad4 ASJ exome AF: 0.297

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.337

Gnomad4 NFE exome AF: 0.287

Gnomad4 OTH exome AF: 0.282

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

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.286

Alfa AF: 0.288 Hom.: 16997

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
MutationTaster	Benign	0.0067	P;P;P
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

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: rs11264875; hg19: chr1-153994647; COSMIC: COSV55145512;