rs17610181

Variant names:

• chr17-61590592-G-A
• rs17610181
• NM_199290.4:c.589C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-61590592-G-A
• chr17-61590592-G-C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_199290.4(NACA2):​c.589C>T​(p.Arg197*) 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
• Publications: 34 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199290.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NACA2	NM_199290.4	MANE Select	c.589C>T	p.Arg197*	stop_gained	Exon 1 of 1	NP_954984.1	Q9H009

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NACA2	ENST00000521764.3	TSL:6 MANE Select	c.589C>T	p.Arg197*	stop_gained	Exon 1 of 1	ENSP00000427802.1	Q9H009

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

GnomAD2 exomes AF: 0.155 AC: 38964 AN: 251482 AF XY: 0.163

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 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

African (AFR) AF: 0.0660 AC: 2211 AN: 33480

American (AMR) AF: 0.104 AC: 4653 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 4706 AN: 26134

East Asian (EAS) AF: 0.163 AC: 6454 AN: 39700

South Asian (SAS) AF: 0.272 AC: 23462 AN: 86240

European-Finnish (FIN) AF: 0.118 AC: 6302 AN: 53418

Middle Eastern (MID) AF: 0.182 AC: 1047 AN: 5768

European-Non Finnish (NFE) AF: 0.150 AC: 166289 AN: 1111696

Other (OTH) AF: 0.160 AC: 9679 AN: 60388

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

African (AFR) AF: 0.0690 AC: 2865 AN: 41494

American (AMR) AF: 0.130 AC: 1993 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 581 AN: 3468

East Asian (EAS) AF: 0.185 AC: 959 AN: 5172

South Asian (SAS) AF: 0.278 AC: 1339 AN: 4820

European-Finnish (FIN) AF: 0.115 AC: 1216 AN: 10578

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.149 AC: 10116 AN: 67972

Other (OTH) AF: 0.155 AC: 327 AN: 2110

Alfa AF: 0.125 Hom.: 1039

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 v4.9

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
PhyloP100		5.3
Vest4		0.056
GERP RS		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=144/56	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: rs17610181; hg19: chr17-59667953; COSMIC: COSV71713121;