16-1834265-T-G

Variant names:

• chr16-1834265-T-G
• rs1429035661
• NM_001163560.3:c.1407A>C

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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
• 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]

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

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.1407A>C	p.Lys469Asn	missense	Exon 14 of 14	NP_001157032.1	Q8N635-2
	MEIOB	NM_152764.3		c.1320A>C	p.Lys440Asn	missense	Exon 13 of 13	NP_689977.2	Q8N635-1
	FAHD1	NM_001018104.3		c.628-3751T>G		intron	N/A	NP_001018114.2	Q6P587-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIOB	ENST00000325962.9	TSL:5 MANE Select	c.1407A>C	p.Lys469Asn	missense	Exon 14 of 14	ENSP00000314484.3	Q8N635-2
	FAHD1	ENST00000382668.8	TSL:1	c.628-4997T>G		intron	N/A	ENSP00000372114.5	Q6P587-2
	MEIOB	ENST00000397344.7	TSL:5	c.1320A>C	p.Lys440Asn	missense	Exon 13 of 13	ENSP00000380504.3	Q8N635-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.023
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.042
Sift	Benign	0.23	T
Sift4G	Benign	0.46	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

Other links and lift over

dbSNP: rs1429035661; hg19: chr16-1884266;