Variant 9-131436625-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013318.4(PRRC2B):c.299G>C(p.Ser100Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PRRC2B
NM_013318.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94

Variant links:

Genes affected

PRRC2B (HGNC:28121): (proline rich coiled-coil 2B) Enables RNA binding activity. Predicted to be involved in cell differentiation. Predicted to act upstream of or within in utero embryonic development. [provided by Alliance of Genome Resources, Apr 2022]

PRRC2B links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21229705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRRC2B	NM_013318.4 linkuse as main transcript	c.299G>C	p.Ser100Thr	missense_variant	4/32	ENST00000683519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Appris	UniProt
PRRC2B	ENST00000683519.1 linkuse as main transcript	c.299G>C	p.Ser100Thr	missense_variant	4/32	NM_013318.4	P2	Q5JSZ5-1
	ENST00000691540.1 linkuse as main transcript	c.42G>C	p.Gln14His	missense_variant	2/5		P1
PRRC2B	ENST00000684596.1 linkuse as main transcript	c.299G>C	p.Ser100Thr	missense_variant	4/32		P2	Q5JSZ5-1
PRRC2B	ENST00000682501.1 linkuse as main transcript	c.299G>C	p.Ser100Thr	missense_variant	4/31		A2	Q5JSZ5-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248516

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS 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:

0.00000137

AC:

AN:

1461090

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726836

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 04, 2024

The c.299G>C (p.S100T) alteration is located in exon 3 (coding exon 3) of the PRRC2B gene. This alteration results from a G to C substitution at nucleotide position 299, causing the serine (S) at amino acid position 100 to be replaced by a threonine (T). 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

0.069

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.;L

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.4

N;.;N

REVEL

Benign

0.071

Sift4G

Benign

0.47

T;.;T

Polyphen

0.99

.;.;D

Vest4

0.39

MutPred

0.34

Gain of glycosylation at S99 (P = 0.0608);Gain of glycosylation at S99 (P = 0.0608);Gain of glycosylation at S99 (P = 0.0608);

MVP

0.14

MPC

0.36

ClinPred

0.67

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over