16-1844958-G-A

Variant names:

• chr16-1844958-G-A
• rs149488366
• NM_001163560.3:c.784C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.22
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• spermatogenic failure 22

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.025820732).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163560.3. 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
	MEIOB	NM_001163560.3	MANE Select	c.784C>T	p.Pro262Ser	missense	Exon 10 of 14	NP_001157032.1	Q8N635-2
	MEIOB	NM_152764.3		c.784C>T	p.Pro262Ser	missense	Exon 10 of 13	NP_689977.2	Q8N635-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIOB	ENST00000325962.9	TSL:5 MANE Select	c.784C>T	p.Pro262Ser	missense	Exon 10 of 14	ENSP00000314484.3	Q8N635-2
	MEIOB	ENST00000397344.7	TSL:5	c.784C>T	p.Pro262Ser	missense	Exon 10 of 13	ENSP00000380504.3	Q8N635-1
	MEIOB	ENST00000470044.5	TSL:2	c.163C>T	p.Pro55Ser	missense	Exon 9 of 13	ENSP00000457416.1	H3BU10

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152038 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.000257 AC: 60 AN: 233560 AF XY: 0.000222

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 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.: 0 Cov.: 18 AF XY: 0.000171 AC XY: 112 AN XY: 653558

African (AFR) AF: 0.00 AC: 0 AN: 29920

American (AMR) AF: 0.000293 AC: 12 AN: 40906

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 64 AN: 24640

East Asian (EAS) AF: 0.00 AC: 0 AN: 37806

South Asian (SAS) AF: 0.0000261 AC: 2 AN: 76774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52528

Middle Eastern (MID) AF: 0.000379 AC: 2 AN: 5274

European-Non Finnish (NFE) AF: 0.000128 AC: 126 AN: 985126

Other (OTH) AF: 0.000366 AC: 20 AN: 54710

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152156 Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16 AN XY: 74390

African (AFR) AF: 0.00 AC: 0 AN: 41520

American (AMR) AF: 0.0000655 AC: 1 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000491 Hom.: 0

Bravo AF: 0.000208

ExAC AF: 0.000223 AC: 27

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	0.13
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.2
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.088
Sift	Benign	0.063	T
Sift4G	Benign	0.069	T
Polyphen		0.82	P
Vest4		0.46
MVP		0.34
ClinPred		0.096	T
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.56
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs149488366; hg19: chr16-1894959;