19-35765143-G-A

Variant names:

• chr19-35765143-G-A
• rs900144714
• NM_001367856.1:c.736G>A

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.736G>A​(p.Asp246Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: PROSER3 NM_001367856.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15
• 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=0.11536029).

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.736G>A	p.Asp246Asn	missense	Exon 7 of 11	NP_001354785.1	A0A2R8Y8D9
	PROSER3	NM_001438802.1		c.733G>A	p.Asp245Asn	missense	Exon 7 of 11	NP_001425731.1
	PROSER3	NM_001395458.1		c.736G>A	p.Asp246Asn	missense	Exon 7 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.736G>A	p.Asp246Asn	missense	Exon 7 of 11	ENSP00000496769.2	A0A2R8Y8D9
	PROSER3	ENST00000396908.10	TSL:1	c.736G>A	p.Asp246Asn	missense	Exon 7 of 11	ENSP00000380116.5
	PROSER3	ENST00000696041.1		c.736G>A	p.Asp246Asn	missense	Exon 7 of 11	ENSP00000512346.1	A0A8Q3WKY3

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152090 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152090 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74288

African (AFR) AF: 0.0000242 AC: 1 AN: 41396

American (AMR) AF: 0.0000655 AC: 1 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.91	T
PhyloP100		1.2
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.096
Sift	Benign	0.25	T
Sift4G	Benign	0.22	T
Vest4		0.073
MutPred		0.14		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.20
ClinPred		0.39	T
GERP RS		3.4
Varity_R		0.054
gMVP		0.062
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs900144714; hg19: chr19-36256044;