NM_153256.4:c.322A>G

Variant names:

• chr10-11866714-A-G
• NM_153256.4:c.322A>G

Variant summary

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

The NM_153256.4(PROSER2):​c.322A>G​(p.Ile108Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PROSER2 NM_153256.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.64
• Publications: 0 publications found

Genes affected

PROSER2 (HGNC:23728): (proline and serine rich 2)

PROSER2-AS1 (HGNC:27343): (PROSER2 antisense RNA 1)

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=0.16713965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROSER2	NM_153256.4	c.322A>G	p.Ile108Val	missense_variant	Exon 3 of 4	ENST00000277570.10	NP_694988.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROSER2	ENST00000277570.10	c.322A>G	p.Ile108Val	missense_variant	Exon 3 of 4	1	NM_153256.4	ENSP00000277570.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 02, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.322A>G (p.I108V) alteration is located in exon 3 (coding exon 2) of the PROSER2 gene. This alteration results from a A to G substitution at nucleotide position 322, causing the isoleucine (I) at amino acid position 108 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	.;T
Eigen	Benign	0.047
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
PhyloP100		5.6
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.37	.;N
REVEL	Benign	0.10
Sift	Benign	0.089	.;T
Sift4G	Benign	0.46	T;T
Polyphen		0.56	.;P
Vest4		0.21
MutPred		0.16		Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.17
MPC		0.35
ClinPred		0.55	D
GERP RS		4.2
Varity_R		0.023
gMVP		0.22
Mutation Taster		=92/8	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

hg19: chr10-11908713;