Variant 16-1844958-G-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_001163560.3(MEIOB):c.784C>T(p.Pro262Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000176 in 1,459,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

MEIOB
NM_001163560.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.22

Variant links:

Genes affected

MEIOB (HGNC:28569): (meiosis specific with OB-fold) Predicted to enable chromatin binding activity; single-stranded DNA 3'-5' exodeoxyribonuclease activity; and single-stranded DNA binding activity. Predicted to be involved in double-strand break repair via homologous recombination; fertilization; and meiotic nuclear division. Predicted to be located in cytoplasm. Implicated in spermatogenic failure 22. [provided by Alliance of Genome Resources, Apr 2022]

MEIOB links:

(HGNC:):

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=0.025820732).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEIOB	NM_001163560.3 linkuse as main transcript	c.784C>T	p.Pro262Ser	missense_variant	10/14	ENST00000325962.9	NP_001157032.1
MEIOB	NM_152764.3 linkuse as main transcript	c.784C>T	p.Pro262Ser	missense_variant	10/13		NP_689977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEIOB	ENST00000325962.9 linkuse as main transcript	c.784C>T	p.Pro262Ser	missense_variant	10/14	5	NM_001163560.3	ENSP00000314484	P1	Q8N635-2
	ENST00000470044.5 linkuse as main transcript	c.163C>T	p.Pro55Ser	missense_variant	9/13	2		ENSP00000457416	P1
MEIOB	ENST00000397344.7 linkuse as main transcript	c.784C>T	p.Pro262Ser	missense_variant	10/13	5		ENSP00000380504		Q8N635-1
MEIOB	ENST00000496541.6 linkuse as main transcript			downstream_gene_variant		5		ENSP00000456880

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000257

AC:

AN:

233560

Hom.:

AF XY:

0.000222

AC XY:

AN XY:

126406

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000294

Gnomad ASJ exome

AF:

0.00302

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.000351

GnomAD4 exome

AF:

0.000173

AC:

226

AN:

1307684

Hom.:

Cov.:

AF XY:

0.000171

AC XY:

112

AN XY:

653558

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000293

Gnomad4 ASJ exome

AF:

0.00260

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000261

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000128

Gnomad4 OTH exome

AF:

0.000366

GnomAD4 genome

AF:

0.000204

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000491

Hom.:

Bravo

AF:

0.000208

ExAC

AF:

0.000223

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

Apr 25, 2022

The c.784C>T (p.P262S) alteration is located in exon 10 (coding exon 9) of the MEIOB gene. This alteration results from a C to T substitution at nucleotide position 784, causing the proline (P) at amino acid position 262 to be replaced by a serine (S). 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

0.13

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.091

T;.;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.4

.;M;M

MutationTaster

Benign

0.80

N;N;N;N;N

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Benign

0.088

Sift

Benign

0.063

T;T;T

Sift4G

Benign

0.069

T;T;T

Polyphen

0.82

.;.;P

Vest4

0.46

MVP

0.34

ClinPred

0.096

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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