16-1841900-ATC-GTG

Variant names:

• chr16-1841900-ATC-GTG
• NM_001163560.3:c.952_954delGATinsCAC
• MEIOB p.Asp318His

Variant summary

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

The NM_001163560.3(MEIOB):​c.952_954delGATinsCAC​(p.Asp318His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. D318Y) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MEIOB NM_001163560.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77
• Publications: 0 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.

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.952_954delGATinsCAC	p.Asp318His	missense	N/A	NP_001157032.1	Q8N635-2
	MEIOB	NM_152764.3		c.952_954delGATinsCAC	p.Asp318His	missense	N/A	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.952_954delGATinsCAC	p.Asp318His	missense	N/A	ENSP00000314484.3	Q8N635-2
	MEIOB	ENST00000397344.7	TSL:5	c.952_954delGATinsCAC	p.Asp318His	missense	N/A	ENSP00000380504.3	Q8N635-1
	MEIOB	ENST00000470044.5	TSL:2	c.331_333delGATinsCAC	p.Asp111His	missense	N/A	ENSP00000457416.1	H3BU10

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-1891901;