Genetic Variant BOLL:p.Ser204Pro (chr2-197756547-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_033030.6(BOLL):c.610T>C(p.Ser204Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,452,360 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: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BOLL
NM_033030.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.43

Variant links:

Genes affected

BOLL (HGNC:14273): (boule homolog, RNA binding protein) This gene belongs to the DAZ gene family required for germ cell development. It encodes an RNA-binding protein which is more similar to Drosophila Boule than to human proteins encoded by genes DAZ (deleted in azoospermia) or DAZL (deleted in azoospermia-like). Loss of this gene function results in the absence of sperm in semen (azoospermia). Histological studies demonstrated that the primary defect is at the meiotic G2/M transition. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

BOLL links:

ENSG00000222017 (HGNC:):

ENSG00000222017 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31160665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BOLL	NM_033030.6 link	c.610T>C	p.Ser204Pro	missense_variant	Exon 9 of 11	ENST00000392296.9	NP_149019.1	Q8N9W6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BOLL	ENST00000392296.9 link	c.610T>C	p.Ser204Pro	missense_variant	Exon 9 of 11	1	NM_033030.6	ENSP00000376116.4		Q8N9W6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000837

AC:

AN:

238836

Hom.:

AF XY:

0.00000773

AC XY:

AN XY:

129402

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000114

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:

0.00000138

AC:

AN:

1452360

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722328

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000507

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:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.646T>C (p.S216P) alteration is located in exon 9 (coding exon 9) of the BOLL gene. This alteration results from a T to C substitution at nucleotide position 646, causing the serine (S) at amino acid position 216 to be replaced by a proline (P). 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

0.072

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

T;T;.;.;T

Eigen

Benign

0.039

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.79

T;.;T;T;T

M_CAP

Benign

0.0087

MetaRNN

Benign

0.31

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

.;N;.;.;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.60

N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.25

T;T;T;T;T

Sift4G

Benign

0.23

T;T;T;T;T

Polyphen

0.53, 0.18

.;P;.;B;P

Vest4

0.62

MutPred

0.29

.;Gain of glycosylation at S204 (P = 0.0345);.;.;Gain of glycosylation at S204 (P = 0.0345);

MVP

0.27

MPC

0.83

ClinPred

0.44

GERP RS

5.7

Varity_R

0.25

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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