16-1844960-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001163560.3(MEIOB):ā€‹c.782T>Cā€‹(p.Ile261Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,412,474 control chromosomes in the GnomAD database, including 19,038 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.18 ( 2573 hom., cov: 32)
Exomes š‘“: 0.16 ( 16465 hom. )

Consequence

MEIOB
NM_001163560.3 missense

Scores

18

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.50
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0021336675).
BP6
Variant 16-1844960-A-G is Benign according to our data. Variant chr16-1844960-A-G is described in ClinVar as [Benign]. Clinvar id is 1228722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MEIOBNM_001163560.3 linkuse as main transcriptc.782T>C p.Ile261Thr missense_variant 10/14 ENST00000325962.9 NP_001157032.1
MEIOBNM_152764.3 linkuse as main transcriptc.782T>C p.Ile261Thr missense_variant 10/13 NP_689977.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MEIOBENST00000325962.9 linkuse as main transcriptc.782T>C p.Ile261Thr missense_variant 10/145 NM_001163560.3 ENSP00000314484 P1Q8N635-2
ENST00000470044.5 linkuse as main transcriptc.161T>C p.Ile54Thr missense_variant 9/132 ENSP00000457416 P1
MEIOBENST00000397344.7 linkuse as main transcriptc.782T>C p.Ile261Thr missense_variant 10/135 ENSP00000380504 Q8N635-1
MEIOBENST00000496541.6 linkuse as main transcriptc.161T>C p.Ter54= incomplete_terminal_codon_variant, coding_sequence_variant 8/85 ENSP00000456880

Frequencies

GnomAD3 genomes
AF:
0.178
AC:
27084
AN:
152054
Hom.:
2572
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.174
Gnomad AMI
AF:
0.221
Gnomad AMR
AF:
0.187
Gnomad ASJ
AF:
0.129
Gnomad EAS
AF:
0.165
Gnomad SAS
AF:
0.272
Gnomad FIN
AF:
0.271
Gnomad MID
AF:
0.111
Gnomad NFE
AF:
0.162
Gnomad OTH
AF:
0.149
GnomAD3 exomes
AF:
0.177
AC:
40380
AN:
227970
Hom.:
3871
AF XY:
0.182
AC XY:
22461
AN XY:
123424
show subpopulations
Gnomad AFR exome
AF:
0.169
Gnomad AMR exome
AF:
0.157
Gnomad ASJ exome
AF:
0.126
Gnomad EAS exome
AF:
0.141
Gnomad SAS exome
AF:
0.276
Gnomad FIN exome
AF:
0.259
Gnomad NFE exome
AF:
0.155
Gnomad OTH exome
AF:
0.166
GnomAD4 exome
AF:
0.155
AC:
195624
AN:
1260300
Hom.:
16465
Cov.:
17
AF XY:
0.160
AC XY:
100749
AN XY:
629962
show subpopulations
Gnomad4 AFR exome
AF:
0.162
Gnomad4 AMR exome
AF:
0.166
Gnomad4 ASJ exome
AF:
0.125
Gnomad4 EAS exome
AF:
0.187
Gnomad4 SAS exome
AF:
0.265
Gnomad4 FIN exome
AF:
0.250
Gnomad4 NFE exome
AF:
0.140
Gnomad4 OTH exome
AF:
0.156
GnomAD4 genome
AF:
0.178
AC:
27102
AN:
152174
Hom.:
2573
Cov.:
32
AF XY:
0.186
AC XY:
13845
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.174
Gnomad4 AMR
AF:
0.187
Gnomad4 ASJ
AF:
0.129
Gnomad4 EAS
AF:
0.165
Gnomad4 SAS
AF:
0.271
Gnomad4 FIN
AF:
0.271
Gnomad4 NFE
AF:
0.162
Gnomad4 OTH
AF:
0.148
Alfa
AF:
0.160
Hom.:
4797
Bravo
AF:
0.166
TwinsUK
AF:
0.159
AC:
590
ALSPAC
AF:
0.159
AC:
613
ESP6500AA
AF:
0.180
AC:
789
ESP6500EA
AF:
0.154
AC:
1319
ExAC
AF:
0.184
AC:
22278
Asia WGS
AF:
0.254
AC:
883
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxApr 19, 2019This variant is associated with the following publications: (PMID: 30679340) -
MEIOB-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesOct 23, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.053
BayesDel_addAF
Benign
-0.78
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
15
DANN
Benign
0.66
DEOGEN2
Benign
0.012
T;.;T
Eigen
Benign
-0.95
Eigen_PC
Benign
-0.66
FATHMM_MKL
Benign
0.019
N
LIST_S2
Benign
0.40
T;T;T
MetaRNN
Benign
0.0021
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-2.7
.;N;N
MutationTaster
Benign
1.0
P;P;P;P;P
PrimateAI
Benign
0.47
T
PROVEAN
Benign
1.9
N;N;N
REVEL
Benign
0.072
Sift
Benign
1.0
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0
.;.;B
Vest4
0.098
ClinPred
0.0018
T
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.044
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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.

Other links and lift over

dbSNP: rs9806945; hg19: chr16-1894961; COSMIC: COSV58055712; COSMIC: COSV58055712; API