16-1844960-A-G

Position:

• chr16-1844960-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001163560.3(MEIOB):​c.782T>C​(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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.18 (2573 hom., cov: 32)
  • Exomes 𝑓: 0.16 (16465 hom.)
• Consequence: MEIOB NM_001163560.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.50

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]

(HGNC:):

ACMG classification

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	UniProt
MEIOB	NM_001163560.3	c.782T>C	p.Ile261Thr	missense_variant	10/14	ENST00000325962.9
MEIOB	NM_152764.3	c.782T>C	p.Ile261Thr	missense_variant	10/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEIOB	ENST00000325962.9	c.782T>C	p.Ile261Thr	missense_variant	10/14	5	NM_001163560.3	P1
	ENST00000470044.5	c.161T>C	p.Ile54Thr	missense_variant	9/13	2		P1
MEIOB	ENST00000397344.7	c.782T>C	p.Ile261Thr	missense_variant	10/13	5
MEIOB	ENST00000496541.6	c.161T>C	p.Ter54=	incomplete_terminal_codon_variant, coding_sequence_variant	8/8	5

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27084 AN: 152054 Hom.: 2572 Cov.: 32

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

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

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

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2019	This variant is associated with the following publications: (PMID: 30679340) -

MEIOB-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 23, 2019

This 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

Other links and lift over

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