15-68780122-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_006305.4(ANP32A):c.709C>A(p.Arg237=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00259 in 1,613,416 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (59 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (39 hom.)
• Consequence: ANP32A NM_006305.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.91

Genes affected

ANP32A (HGNC:13233): (acidic nuclear phosphoprotein 32 family member A) Enables RNA binding activity. Involved in nucleocytoplasmic transport. Located in endoplasmic reticulum; nucleus; and perinuclear region of cytoplasm. [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 (BayesDel_noAF=-0.4).
• BP6: Variant 15-68780122-G-T is Benign according to our data. Variant chr15-68780122-G-T is described in ClinVar as [Benign]. Clinvar id is 776919.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0141 (2148/152044) while in subpopulation AFR AF= 0.0492 (2037/41430). AF 95% confidence interval is 0.0474. There are 59 homozygotes in gnomad4. There are 1001 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANP32A	NM_006305.4	c.709C>A	p.Arg237=	synonymous_variant	7/7	ENST00000465139.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANP32A	ENST00000465139.6	c.709C>A	p.Arg237=	synonymous_variant	7/7	1	NM_006305.4	P2

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2140 AN: 151926 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.0491

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00472

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0101

GnomAD3 exomes AF: 0.00340 AC: 843 AN: 248304 Hom.: 16 AF XY: 0.00245 AC XY: 329 AN XY: 134446

Gnomad AFR exome AF: 0.0453

Gnomad AMR exome AF: 0.00217

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000208

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00139 AC: 2029 AN: 1461372 Hom.: 39 Cov.: 31 AF XY: 0.00115 AC XY: 835 AN XY: 727000

Gnomad4 AFR exome AF: 0.0464

Gnomad4 AMR exome AF: 0.00233

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000136

Gnomad4 OTH exome AF: 0.00312

GnomAD4 genome AF: 0.0141 AC: 2148 AN: 152044 Hom.: 59 Cov.: 32 AF XY: 0.0135 AC XY: 1001 AN XY: 74318

Gnomad4 AFR AF: 0.0492

Gnomad4 AMR AF: 0.00471

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.00995

Alfa AF: 0.00778 Hom.: 11

Bravo AF: 0.0160

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	9.4
Dann	Benign	0.65
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8

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: rs77729713; hg19: chr15-69072461;