16-1841902-C-G

Variant names:

• chr16-1841902-C-G
• rs75546096
• NM_001163560.3:c.952G>C

Variant summary

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

The NM_001163560.3(MEIOB):​c.952G>C​(p.Asp318His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MEIOB NM_001163560.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68

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]

ENSG00000260541 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3324831).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEIOB	NM_001163560.3	c.952G>C	p.Asp318His	missense_variant	Exon 11 of 14	ENST00000325962.9	NP_001157032.1
MEIOB	NM_152764.3	c.952G>C	p.Asp318His	missense_variant	Exon 11 of 13		NP_689977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEIOB	ENST00000325962.9	c.952G>C	p.Asp318His	missense_variant	Exon 11 of 14	5	NM_001163560.3	ENSP00000314484.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455350 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 723868

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.080	T;.;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.1	.;M;M
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.013	D;D;D
Sift4G	Uncertain	0.019	D;D;D
Polyphen		0.81	.;.;P
Vest4		0.38
MutPred		0.49		.;Loss of ubiquitination at K316 (P = 0.0236);Loss of ubiquitination at K316 (P = 0.0236);
MVP		0.30
ClinPred		0.93	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.46

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

Other links and lift over

dbSNP: rs75546096; hg19: chr16-1891903;