16-1841842-T-C

Variant names:

• chr16-1841842-T-C
• rs138046004
• NM_001163560.3:c.1012A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001163560.3(MEIOB):​c.1012A>G​(p.Thr338Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,434,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T338P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: MEIOB NM_001163560.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.351
• Publications: 2 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

ENSG00000260541 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.069009066).

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.1012A>G	p.Thr338Ala	missense	Exon 11 of 14	NP_001157032.1	Q8N635-2
	MEIOB	NM_152764.3		c.1012A>G	p.Thr338Ala	missense	Exon 11 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.1012A>G	p.Thr338Ala	missense	Exon 11 of 14	ENSP00000314484.3	Q8N635-2
	MEIOB	ENST00000397344.7	TSL:5	c.1012A>G	p.Thr338Ala	missense	Exon 11 of 13	ENSP00000380504.3	Q8N635-1
	MEIOB	ENST00000470044.5	TSL:2	c.391A>G	p.Thr131Ala	missense	Exon 10 of 13	ENSP00000457416.1	H3BU10

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000858 AC: 2 AN: 233224 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000183

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000279 AC: 4 AN: 1434468 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 711784

African (AFR) AF: 0.00 AC: 0 AN: 32420

American (AMR) AF: 0.00 AC: 0 AN: 39696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25420

East Asian (EAS) AF: 0.00 AC: 0 AN: 39158

South Asian (SAS) AF: 0.00 AC: 0 AN: 79366

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52986

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5582

European-Non Finnish (NFE) AF: 0.00000363 AC: 4 AN: 1100450

Other (OTH) AF: 0.00 AC: 0 AN: 59390

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.93
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.35
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.097
Sift	Benign	0.27	T
Sift4G	Benign	0.18	T
Polyphen		0.0010	B
Vest4		0.14
MutPred		0.48		Loss of sheet (P = 0.0084)
MVP		0.030
ClinPred		0.045	T
GERP RS		-0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.046
gMVP		0.24

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

Other links and lift over

dbSNP: rs138046004; hg19: chr16-1891843;