16-1834265-T-G

Position:

• chr16-1834265-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001163560.3(MEIOB):​c.1407A>C​(p.Lys469Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MEIOB NM_001163560.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0230

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:):

FAHD1 (HGNC:14169): (fumarylacetoacetate hydrolase domain containing 1) Enables acetylpyruvate hydrolase activity; fumarylpyruvate hydrolase activity; and oxaloacetate decarboxylase activity. Located in cytosol; mitochondrion; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045711458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEIOB	NM_001163560.3	c.1407A>C	p.Lys469Asn	missense_variant	14/14	ENST00000325962.9	NP_001157032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEIOB	ENST00000325962.9	c.1407A>C	p.Lys469Asn	missense_variant	14/14	5	NM_001163560.3	ENSP00000314484	P1
	ENST00000470044.5	c.786A>C	p.Lys262Asn	missense_variant	13/13	2		ENSP00000457416	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 31

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

Sep 22, 2023

The c.1407A>C (p.K469N) alteration is located in exon 14 (coding exon 13) of the MEIOB gene. This alteration results from a A to C substitution at nucleotide position 1407, causing the lysine (K) at amino acid position 469 to be replaced by an asparagine (N). 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	Benign	0.084
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.88
DANN	Benign	0.61
DEOGEN2	Benign	0.0069	T;.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.30	T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.046	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	.;.;N
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.35	N;N;N
REVEL	Benign	0.042
Sift	Benign	0.23	T;T;T
Sift4G	Benign	0.46	T;T;T
Polyphen		0.0010	.;.;B
Vest4		0.089
MutPred		0.13		.;.;Loss of ubiquitination at K440 (P = 0.0051);
MVP		0.014
ClinPred		0.10	T
GERP RS		-3.8
Varity_R		0.052
gMVP		0.27

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: chr16-1884266;