19-35771026-A-G

Position:

• chr19-35771026-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367856.1(PROSER3):​c.*2481A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,044 control chromosomes in the GnomAD database, including 3,920 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 0.22 (3920 hom., cov: 32)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: PROSER3 NM_001367856.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

Genes affected

PROSER3 (HGNC:25204): (proline and serine rich 3)

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROSER3	NM_001367856.1	c.*2481A>G		3_prime_UTR_variant	11/11	ENST00000646935.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROSER3	ENST00000646935.2	c.*2481A>G		3_prime_UTR_variant	11/11		NM_001367856.1	P3
PROSER3	ENST00000396908.9	c.*2481A>G		3_prime_UTR_variant	11/11	1		A2
	ENST00000589397.1	n.3T>C		non_coding_transcript_exon_variant	1/2	5
PROSER3	ENST00000544158.2	n.1072A>G		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33559 AN: 151920 Hom.: 3920 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.216

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.221 AC: 33582 AN: 152038 Hom.: 3920 Cov.: 32 AF XY: 0.226 AC XY: 16809 AN XY: 74322

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.214

Alfa AF: 0.184 Hom.: 4357

Bravo AF: 0.233

Asia WGS AF: 0.270 AC: 939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.5
DANN	Benign	0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10420134; hg19: chr19-36261928;