chr16-1844951-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting

The NM_001163560.3(MEIOB):c.791C>G(p.Ala264Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000173 in 1,503,048 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000067 ( 0 hom. )

Consequence

MEIOB
NM_001163560.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.98

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:

Genome browser will be placed here

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;

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000112 (17/152150) while in subpopulation AFR AF= 0.000362 (15/41442). AF 95% confidence interval is 0.000222. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEIOB	NM_001163560.3 link	c.791C>G	p.Ala264Gly	missense_variant	Exon 10 of 14	ENST00000325962.9	NP_001157032.1	Q8N635-2
MEIOB	NM_152764.3 link	c.791C>G	p.Ala264Gly	missense_variant	Exon 10 of 13		NP_689977.2	Q8N635-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MEIOB	ENST00000325962.9 link	c.791C>G	p.Ala264Gly	missense_variant	Exon 10 of 14	5	NM_001163560.3	ENSP00000314484.3	Q8N635-2
MEIOB	ENST00000397344.7 link	c.791C>G	p.Ala264Gly	missense_variant	Exon 10 of 13	5		ENSP00000380504.3	Q8N635-1
ENSG00000289722	ENST00000470044.5 link	c.170C>G	p.Ala57Gly	missense_variant	Exon 9 of 13	2		ENSP00000457416.1	H3BU10
MEIOB	ENST00000496541.6 link	c.*9C>G		downstream_gene_variant		5		ENSP00000456880.1	H3BSU6

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000842

AC:

AN:

237412

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128288

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000635

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000666

AC:

AN:

1350898

Hom.:

Cov.:

AF XY:

0.00000445

AC XY:

AN XY:

673910

show subpopulations

Gnomad4 AFR exome

AF:

0.000194

Gnomad4 AMR exome

AF:

0.0000477

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000261

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

AF:

0.000112

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000117

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.791C>G (p.A264G) alteration is located in exon 10 (coding exon 9) of the MEIOB gene. This alteration results from a C to G substitution at nucleotide position 791, causing the alanine (A) at amino acid position 264 to be replaced by a glycine (G). 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

-0.048

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.;T

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.57

D;D;D

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.7

.;M;M

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.010

D;D;D

Sift4G

Uncertain

0.012

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.61

MVP

0.26

ClinPred

0.85

GERP RS

6.0

Varity_R

0.38

gMVP

0.79

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