19-35764942-C-T

Variant names:

• chr19-35764942-C-T
• rs116923661
• NM_001367856.1:c.626+6C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001367856.1(PROSER3):​c.626+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,613,440 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (8 hom., cov: 31)
  • Exomes 𝑓: 0.011 (97 hom.)
• Consequence: PROSER3 NM_001367856.1 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.559
• Publications: 1 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-35764942-C-T is Benign according to our data. Variant chr19-35764942-C-T is described in ClinVar as Benign. ClinVar VariationId is 3770538.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367856.1. 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
	PROSER3	NM_001367856.1	MANE Select	c.626+6C>T		splice_region intron	N/A	NP_001354785.1	A0A2R8Y8D9
	PROSER3	NM_001438802.1		c.623+6C>T		splice_region intron	N/A	NP_001425731.1
	PROSER3	NM_001395458.1		c.626+6C>T		splice_region intron	N/A	NP_001382387.1	A0A2R8Y8D9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROSER3	ENST00000646935.2	MANE Select	c.626+6C>T		splice_region intron	N/A	ENSP00000496769.2	A0A2R8Y8D9
	PROSER3	ENST00000396908.10	TSL:1	c.626+6C>T		splice_region intron	N/A	ENSP00000380116.5
	PROSER3	ENST00000696041.1		c.626+6C>T		splice_region intron	N/A	ENSP00000512346.1	A0A8Q3WKY3

Frequencies

GnomAD3 genomes AF: 0.00762 AC: 1160 AN: 152146 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.00203

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00956

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00787

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0121

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00792 AC: 1969 AN: 248678 AF XY: 0.00861

Gnomad AFR exome AF: 0.00239

Gnomad AMR exome AF: 0.00443

Gnomad ASJ exome AF: 0.00875

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00322

Gnomad NFE exome AF: 0.0119

Gnomad OTH exome AF: 0.00878

GnomAD4 exome AF: 0.0107 AC: 15616 AN: 1461176 Hom.: 97 Cov.: 32 AF XY: 0.0108 AC XY: 7839 AN XY: 726918

African (AFR) AF: 0.00218 AC: 73 AN: 33480

American (AMR) AF: 0.00534 AC: 239 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00876 AC: 229 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00793 AC: 684 AN: 86258

European-Finnish (FIN) AF: 0.00408 AC: 216 AN: 52968

Middle Eastern (MID) AF: 0.0102 AC: 59 AN: 5768

European-Non Finnish (NFE) AF: 0.0121 AC: 13490 AN: 1111778

Other (OTH) AF: 0.0104 AC: 625 AN: 60364

GnomAD4 genome AF: 0.00760 AC: 1157 AN: 152264 Hom.: 8 Cov.: 31 AF XY: 0.00766 AC XY: 570 AN XY: 74448

African (AFR) AF: 0.00202 AC: 84 AN: 41564

American (AMR) AF: 0.00955 AC: 146 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00779 AC: 27 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00788 AC: 38 AN: 4822

European-Finnish (FIN) AF: 0.00292 AC: 31 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0120 AC: 817 AN: 68012

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00790 Hom.: 4

Bravo AF: 0.00771

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0147

EpiControl AF: 0.0139

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.54
PhyloP100		0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs116923661; hg19: chr19-36255843;