rs9449648

chr6-83514041-G-A

Variant summary

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

The NM_153362.3(PRSS35):c.-21+1347G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,126 control chromosomes in the GnomAD database, including 2,031 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 0.16 (2031 hom., cov: 32)
• Consequence: PRSS35 NM_153362.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156

Genes affected

PRSS35 (HGNC:21387): (serine protease 35) Predicted to be located in extracellular region. [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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRSS35	NM_153362.3	c.-21+1347G>A		intron_variant		ENST00000369700.4
PRSS35	NM_001170423.2	c.-126+1347G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRSS35	ENST00000369700.4	c.-21+1347G>A		intron_variant		1	NM_153362.3	P1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24008 AN: 152008 Hom.: 2033 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.148

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.158 AC: 24016 AN: 152126 Hom.: 2031 Cov.: 32 AF XY: 0.160 AC XY: 11863 AN XY: 74362

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.147

Alfa AF: 0.157 Hom.: 229

Bravo AF: 0.154

Asia WGS AF: 0.177 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.3
Dann	Benign	0.55

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: rs9449648; hg19: chr6-84223760;