19-35764942-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001367856.1(PROSER3):​c.626+6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PROSER3 NM_001367856.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.559
• Publications: 1 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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>G		splice_region intron	N/A	NP_001354785.1	A0A2R8Y8D9
	PROSER3	NM_001438802.1		c.623+6C>G		splice_region intron	N/A	NP_001425731.1
	PROSER3	NM_001395458.1		c.626+6C>G		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>G		splice_region intron	N/A	ENSP00000496769.2	A0A2R8Y8D9
	PROSER3	ENST00000396908.10	TSL:1	c.626+6C>G		splice_region intron	N/A	ENSP00000380116.5
	PROSER3	ENST00000696041.1		c.626+6C>G		splice_region intron	N/A	ENSP00000512346.1	A0A8Q3WKY3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.51
PhyloP100		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;