Variant 5-139392660-C-T 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.2422G>A(p.Ala808Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000282 in 1,395,526 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 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

PROB1
NM_001161546.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0670

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=0.009846687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PROB1	NM_001161546.2 linkuse as main transcript	c.2422G>A	p.Ala808Thr	missense_variant	1/1	ENST00000434752.4	NP_001155018.1
SPATA24	XM_005271916.5 linkuse as main transcript	c.*3545G>A		3_prime_UTR_variant	6/6		XP_005271973.1
SPATA24	XM_011543252.3 linkuse as main transcript	c.*3545G>A		3_prime_UTR_variant	6/6		XP_011541554.1
SPATA24	XM_011543253.3 linkuse as main transcript	c.*3545G>A		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.2422G>A	p.Ala808Thr	missense_variant	1/1		NM_001161546.2	ENSP00000416033	P1

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

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:

0.000353

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000358

AC:

AN:

27966

Hom.:

AF XY:

0.000378

AC XY:

AN XY:

13216

show subpopulations

Gnomad AFR exome

AF:

0.000617

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000283

AC:

352

AN:

1243346

Hom.:

Cov.:

AF XY:

0.000301

AC XY:

181

AN XY:

600930

show subpopulations

Gnomad4 AFR exome

AF:

0.0000418

Gnomad4 AMR exome

AF:

0.0000798

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000339

Gnomad4 OTH exome

AF:

0.000176

GnomAD4 genome

AF:

0.000276

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.000268

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000387

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

Dec 07, 2021

The c.2422G>A (p.A808T) alteration is located in exon 1 (coding exon 1) of the PROB1 gene. This alteration results from a G to A substitution at nucleotide position 2422, causing the alanine (A) at amino acid position 808 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

0.090

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0021

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.34

M_CAP

Benign

0.011

MetaRNN

Benign

0.0098

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.56

REVEL

Benign

0.022

Sift

Uncertain

0.014

Sift4G

Benign

0.36

Polyphen

0.013

Vest4

0.027

MutPred

0.23

Gain of relative solvent accessibility (P = 0.0082);

MVP

0.014

ClinPred

0.0059

GERP RS

0.87

Varity_R

0.048

gMVP

0.091

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