16-1841878-C-T

Position:

• chr16-1841878-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_001163560.3(MEIOB):​c.976G>A​(p.Ala326Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MEIOB NM_001163560.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.67

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-1841878-C-T is Pathogenic according to our data. Variant chr16-1841878-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 2691778.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.40447357). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEIOB	NM_001163560.3	c.976G>A	p.Ala326Thr	missense_variant	11/14	ENST00000325962.9	NP_001157032.1
MEIOB	NM_152764.3	c.976G>A	p.Ala326Thr	missense_variant	11/13		NP_689977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEIOB	ENST00000325962.9	c.976G>A	p.Ala326Thr	missense_variant	11/14	5	NM_001163560.3	ENSP00000314484.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spermatogenic failure 22 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.37	T;.;T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	.;M;M
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.50
MutPred		0.52		.;Loss of catalytic residue at A326 (P = 0.0905);Loss of catalytic residue at A326 (P = 0.0905);
MVP		0.17
ClinPred		0.99	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.59
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-1891879;