19-35766839-C-G

Variant names:

• chr19-35766839-C-G
• rs978157371
• NM_001367856.1:c.841C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367856.1(PROSER3):​c.841C>G​(p.Arg281Gly) variant causes a missense 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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R281Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PROSER3 NM_001367856.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18568456).

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.841C>G	p.Arg281Gly	missense	Exon 8 of 11	NP_001354785.1	A0A2R8Y8D9
	PROSER3	NM_001438802.1		c.838C>G	p.Arg280Gly	missense	Exon 8 of 11	NP_001425731.1
	PROSER3	NM_001395458.1		c.841C>G	p.Arg281Gly	missense	Exon 8 of 12	NP_001382387.1	A0A2R8Y8D9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROSER3	ENST00000646935.2	MANE Select	c.841C>G	p.Arg281Gly	missense	Exon 8 of 11	ENSP00000496769.2	A0A2R8Y8D9
	PROSER3	ENST00000396908.10	TSL:1	c.841C>G	p.Arg281Gly	missense	Exon 8 of 11	ENSP00000380116.5
	PROSER3	ENST00000696041.1		c.841C>G	p.Arg281Gly	missense	Exon 8 of 11	ENSP00000512346.1	A0A8Q3WKY3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.32
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.066
Sift	Benign	0.10	T
Sift4G	Benign	0.10	T
Vest4		0.29
MutPred		0.17		Loss of MoRF binding (P = 0.0235)
MVP		0.31
ClinPred		0.97	D
GERP RS		2.9
PromoterAI		-0.043	Neutral
Varity_R		0.097
gMVP		0.23
Mutation Taster		=94/6	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: rs978157371; hg19: chr19-36257740;