16-1844928-G-C

Variant names:

• chr16-1844928-G-C
• rs35694423
• NM_001163560.3:c.814C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001163560.3(MEIOB):​c.814C>G​(p.Arg272Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: MEIOB NM_001163560.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEIOB	NM_001163560.3	c.814C>G	p.Arg272Gly	missense_variant	Exon 10 of 14	ENST00000325962.9	NP_001157032.1
MEIOB	NM_152764.3	c.814C>G	p.Arg272Gly	missense_variant	Exon 10 of 13		NP_689977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEIOB	ENST00000325962.9	c.814C>G	p.Arg272Gly	missense_variant	Exon 10 of 14	5	NM_001163560.3	ENSP00000314484.3
MEIOB	ENST00000397344.7	c.814C>G	p.Arg272Gly	missense_variant	Exon 10 of 13	5		ENSP00000380504.3
ENSG00000289722	ENST00000470044.5	c.193C>G	p.Arg65Gly	missense_variant	Exon 9 of 13	2		ENSP00000457416.1
MEIOB	ENST00000496541.6	c.*32C>G		downstream_gene_variant		5		ENSP00000456880.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000415 AC: 1 AN: 240956 Hom.: 0 AF XY: 0.00000768 AC XY: 1 AN XY: 130172

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000308

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399222 Hom.: 0 Cov.: 24 AF XY: 0.00000144 AC XY: 1 AN XY: 696742

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000234

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T;.;T
Eigen	Benign	0.063
Eigen_PC	Benign	0.075
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.5	.;M;M
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.91	.;.;P
Vest4		0.45
MutPred		0.57		.;Gain of loop (P = 0.0051);Gain of loop (P = 0.0051);
MVP		0.21
ClinPred		0.96	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.99		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.99		Position offset: -1
DS_AL_spliceai		0.53		Position offset: 35

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35694423; hg19: chr16-1894929;