NM_001367856.1:c.400C>A

Variant names:

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

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.400C>A​(p.Gln134Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,609,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PROSER3 NM_001367856.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.418
• Publications: 0 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 (MetaRNN=0.023355097).

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>A	p.Gln134Lys	missense	Exon 4 of 11	NP_001354785.1	A0A2R8Y8D9
	PROSER3	NM_001438802.1		c.400C>A	p.Gln134Lys	missense	Exon 4 of 11	NP_001425731.1
	PROSER3	NM_001395458.1		c.400C>A	p.Gln134Lys	missense	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>A	p.Gln134Lys	missense	Exon 4 of 11	ENSP00000496769.2	A0A2R8Y8D9
	PROSER3	ENST00000396908.10	TSL:1	c.400C>A	p.Gln134Lys	missense	Exon 4 of 11	ENSP00000380116.5
	PROSER3	ENST00000537459.5	TSL:1	c.400C>A	p.Gln134Lys	missense	Exon 4 of 5	ENSP00000439886.2	Q2NL68-4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248386 AF XY: 0.00000742

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1457354 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 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: 0.0000116 AC: 1 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: 0.00000451 AC: 5 AN: 1108462

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

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152182 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.000131 AC: 2 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

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	-0.54
CADD	Benign	13
DANN	Benign	0.90
DEOGEN2	Benign	0.034	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.42
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.073
Sift	Benign	0.26	T
Sift4G	Benign	0.27	T
Polyphen		0.0020	B
Vest4		0.29
MutPred		0.26		Gain of methylation at Q134 (P = 0.012)
MVP		0.095
ClinPred		0.022	T
GERP RS		0.76
Varity_R		0.060
gMVP		0.037
Mutation Taster		=98/2	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: rs1052945498; hg19: chr19-36253008;