NM_033030.6:c.595C>T

Variant names:

• chr2-197757358-G-A
• rs1688563014
• NM_033030.6:c.595C>T

Variant summary

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

The NM_033030.6(BOLL):​c.595C>T​(p.Pro199Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P199T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BOLL NM_033030.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.97
• Publications: 0 publications found

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]

ENSG00000222017 (HGNC:):

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=0.16564965).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033030.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BOLL	NM_033030.6	MANE Select	c.595C>T	p.Pro199Ser	missense	Exon 8 of 11	NP_149019.1	Q8N9W6-1
	BOLL	NM_001284361.2		c.679C>T	p.Pro227Ser	missense	Exon 9 of 12	NP_001271290.1	Q8N9W6-2
	BOLL	NM_197970.3		c.631C>T	p.Pro211Ser	missense	Exon 8 of 11	NP_932074.1	Q8N9W6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BOLL	ENST00000392296.9	TSL:1 MANE Select	c.595C>T	p.Pro199Ser	missense	Exon 8 of 11	ENSP00000376116.4	Q8N9W6-1
	BOLL	ENST00000433157.1	TSL:1	c.595C>T	p.Pro199Ser	missense	Exon 8 of 11	ENSP00000396099.1	Q8N9W6-1
	ENSG00000222017	ENST00000409845.1	TSL:1	n.167-14499G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.20
Eigen_PC	Benign	0.015
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N
PhyloP100		3.0
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.041
Sift	Benign	0.11	T
Sift4G	Benign	0.38	T
Polyphen		0.0050	B
Vest4		0.26
MutPred		0.37		Loss of catalytic residue at P199 (P = 0.0764)
MVP		0.25
MPC		0.31
ClinPred		0.37	T
GERP RS		5.3
Varity_R		0.088
gMVP		0.44
Mutation Taster		=86/14	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

dbSNP: rs1688563014; hg19: chr2-198622082;