rs1555472691

Variant names:

• chr16-1862053-T-A
• rs1555472691
• NM_001163560.3:c.191A>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_001163560.3(MEIOB):​c.191A>T​(p.Asn64Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 7.03
• 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]

LINC02124 (HGNC:52981): (long intergenic non-protein coding RNA 2124)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• PP5: Variant 16-1862053-T-A is Pathogenic according to our data. Variant chr16-1862053-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 440759.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEIOB	NM_001163560.3	c.191A>T	p.Asn64Ile	missense_variant	Exon 4 of 14	ENST00000325962.9	NP_001157032.1
MEIOB	NM_152764.3	c.191A>T	p.Asn64Ile	missense_variant	Exon 4 of 13		NP_689977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEIOB	ENST00000325962.9	c.191A>T	p.Asn64Ile	missense_variant	Exon 4 of 14	5	NM_001163560.3	ENSP00000314484.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spermatogenic failure 22 Pathogenic:1

Jan 22, 2024

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	34
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	.;T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	T;T
M_CAP	Uncertain	0.090	D
MetaRNN	Pathogenic	0.94	D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.5	M;M
PhyloP100		7.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-7.9	D;D
REVEL	Uncertain	0.63
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.84
MutPred		0.76		Gain of sheet (P = 0.0011);Gain of sheet (P = 0.0011);
MVP		0.21
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.93
gMVP		0.81
Mutation Taster		=186/114	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.66		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.66		Position offset: -6

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

Other links and lift over

dbSNP: rs1555472691; hg19: chr16-1912054;