chr16-1853075-T-G

Position:

• chr16-1853075-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001163560.3(MEIOB):​c.742A>C​(p.Thr248Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MEIOB NM_001163560.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.37

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEIOB	NM_001163560.3	c.742A>C	p.Thr248Pro	missense_variant	9/14	ENST00000325962.9	NP_001157032.1
MEIOB	NM_152764.3	c.742A>C	p.Thr248Pro	missense_variant	9/13		NP_689977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEIOB	ENST00000325962.9	c.742A>C	p.Thr248Pro	missense_variant	9/14	5	NM_001163560.3	ENSP00000314484	P1
	ENST00000470044.5	c.121A>C	p.Thr41Pro	missense_variant	8/13	2		ENSP00000457416	P1
MEIOB	ENST00000397344.7	c.742A>C	p.Thr248Pro	missense_variant	9/13	5		ENSP00000380504
MEIOB	ENST00000496541.6	c.121A>C	p.Thr41Pro	missense_variant	7/8	5		ENSP00000456880

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2024

The c.742A>C (p.T248P) alteration is located in exon 9 (coding exon 8) of the MEIOB gene. This alteration results from a A to C substitution at nucleotide position 742, causing the threonine (T) at amino acid position 248 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.;T;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.79	T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.70	D;D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.7	.;M;M;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.9	D;D;D;D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.047	D;D;D;.
Polyphen		1.0	.;.;D;.
Vest4		0.76
MutPred		0.56		.;Loss of sheet (P = 7e-04);Loss of sheet (P = 7e-04);.;
MVP		0.21
ClinPred		0.99	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.78
gMVP		0.93

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-1903076;