chr19-35762107-C-T

Variant names:

• chr19-35762107-C-T
• rs1052945498
• NM_001367856.1:c.400C>T

Variant summary

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

The NM_001367856.1(PROSER3):​c.400C>T​(p.Gln134*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PROSER3 NM_001367856.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.418
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.400C>T	p.Gln134*	stop_gained	Exon 4 of 11	NP_001354785.1	A0A2R8Y8D9
	PROSER3	NM_001438802.1		c.400C>T	p.Gln134*	stop_gained	Exon 4 of 11	NP_001425731.1
	PROSER3	NM_001395458.1		c.400C>T	p.Gln134*	stop_gained	Exon 4 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.400C>T	p.Gln134*	stop_gained	Exon 4 of 11	ENSP00000496769.2	A0A2R8Y8D9
	PROSER3	ENST00000396908.10	TSL:1	c.400C>T	p.Gln134*	stop_gained	Exon 4 of 11	ENSP00000380116.5
	PROSER3	ENST00000537459.5	TSL:1	c.400C>T	p.Gln134*	stop_gained	Exon 4 of 5	ENSP00000439886.2	Q2NL68-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457354 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723982

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39524

South Asian (SAS) AF: 0.00 AC: 0 AN: 86056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108462

Other (OTH) AF: 0.00 AC: 0 AN: 60144

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	33
DANN	Uncertain	0.99
Eigen	Benign	0.038
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.034	N
PhyloP100		0.42
Vest4		0.28
GERP RS		0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=106/94	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1052945498; hg19: chr19-36253008;