chr17-61590592-G-A

Position:

• chr17-61590592-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_199290.4(NACA2):​c.589C>T​(p.Arg197Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.151 in 1,613,650 control chromosomes in the GnomAD database, including 20,131 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1436 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18695 hom.)
• Consequence: NACA2 NM_199290.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.26

Genes affected

NACA2 (HGNC:23290): (nascent polypeptide associated complex subunit alpha 2) Predicted to enable unfolded protein binding activity. Predicted to be involved in protein targeting to membrane. Predicted to be located in nucleus. Predicted to be part of nascent polypeptide-associated complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NACA2	NM_199290.4	c.589C>T	p.Arg197Ter	stop_gained	1/1	ENST00000521764.3	NP_954984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NACA2	ENST00000521764.3	c.589C>T	p.Arg197Ter	stop_gained	1/1		NM_199290.4	ENSP00000427802	P1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19545 AN: 151982 Hom.: 1441 Cov.: 32

Gnomad AFR AF: 0.0692

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.154

GnomAD3 exomes AF: 0.155 AC: 38964 AN: 251482 Hom.: 3514 AF XY: 0.163 AC XY: 22198 AN XY: 135918

Gnomad AFR exome AF: 0.0683

Gnomad AMR exome AF: 0.105

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.196

Gnomad SAS exome AF: 0.273

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.148

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.154 AC: 224803 AN: 1461548 Hom.: 18695 Cov.: 34 AF XY: 0.158 AC XY: 114891 AN XY: 727088

Gnomad4 AFR exome AF: 0.0660

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.128 AC: 19540 AN: 152102 Hom.: 1436 Cov.: 32 AF XY: 0.130 AC XY: 9671 AN XY: 74374

Gnomad4 AFR AF: 0.0690

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.155

Alfa AF: 0.127 Hom.: 668

Bravo AF: 0.126

TwinsUK AF: 0.162 AC: 599

ALSPAC AF: 0.155 AC: 596

ESP6500AA AF: 0.0747 AC: 329

ESP6500EA AF: 0.145 AC: 1249

ExAC AF: 0.156 AC: 18980

Asia WGS AF: 0.229 AC: 795 AN: 3478

EpiCase AF: 0.160

EpiControl AF: 0.165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Uncertain	0.54
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.54	D
MutationTaster	Benign	0.000016	P
Vest4		0.056
GERP RS		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs17610181; hg19: chr17-59667953; COSMIC: COSV71713121;