Variant 5-139392711-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001161546.2(PROB1):c.2371G>T(p.Val791Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000536 in 1,407,718 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 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00057 ( 0 hom. )

Consequence

PROB1
NM_001161546.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.57

Variant links:

Genes affected

PROB1 (HGNC:41906): (proline rich basic protein 1) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PROB1 links:

SPATA24 (HGNC:):

SPATA24 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01854375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PROB1	NM_001161546.2 linkuse as main transcript	c.2371G>T	p.Val791Leu	missense_variant	1/1	ENST00000434752.4	NP_001155018.1
SPATA24	XM_005271916.5 linkuse as main transcript	c.*3494G>T		3_prime_UTR_variant	6/6		XP_005271973.1
SPATA24	XM_011543252.3 linkuse as main transcript	c.*3494G>T		3_prime_UTR_variant	6/6		XP_011541554.1
SPATA24	XM_011543253.3 linkuse as main transcript	c.*3494G>T		3_prime_UTR_variant	6/6		XP_011541555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROB1	ENST00000434752.4 linkuse as main transcript	c.2371G>T	p.Val791Leu	missense_variant	1/1		NM_001161546.2	ENSP00000416033	P1

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000239

AC:

AN:

37640

Hom.:

AF XY:

0.000270

AC XY:

AN XY:

18536

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000208

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000120

Gnomad NFE exome

AF:

0.000472

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000569

AC:

714

AN:

1255546

Hom.:

Cov.:

AF XY:

0.000568

AC XY:

345

AN XY:

607004

show subpopulations

Gnomad4 AFR exome

AF:

0.0000816

Gnomad4 AMR exome

AF:

0.000211

Gnomad4 ASJ exome

AF:

0.0000567

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000239

Gnomad4 NFE exome

AF:

0.000671

Gnomad4 OTH exome

AF:

0.000523

GnomAD4 genome

AF:

0.000263

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.000474

Bravo

AF:

0.000310

ExAC

AF:

0.0000549

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

Aug 09, 2021

The c.2371G>T (p.V791L) alteration is located in exon 1 (coding exon 1) of the PROB1 gene. This alteration results from a G to T substitution at nucleotide position 2371, causing the valine (V) at amino acid position 791 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.0050

DANN

Benign

0.81

DEOGEN2

Benign

0.0011

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.33

M_CAP

Benign

0.010

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.10

REVEL

Benign

0.015

Sift

Benign

0.47

Sift4G

Benign

0.50

Polyphen

0.0

Vest4

0.025

MutPred

0.15

Loss of MoRF binding (P = 0.1084);

MVP

0.014

ClinPred

0.029

GERP RS

-5.4

Varity_R

0.041

gMVP

0.044

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

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