chr15-73473916-C-G

Variant names:

• chr15-73473916-C-G
• rs373897163
• NM_001042367.2:c.244C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042367.2(REC114):​c.244C>G​(p.Leu82Val) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: REC114 NM_001042367.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

Genes affected

REC114 (HGNC:25065): (REC114 meiotic recombination protein) The protein encoded by this gene is orthologous to the mouse meiotic recombination protein REC114, which is involved in DNA double-strand break formation during meiosis. The encoded protein is conserved in most eukaryotes and was first discovered and characterized in yeast. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20488769).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REC114	NM_001042367.2	c.244C>G	p.Leu82Val	missense_variant	Exon 2 of 6	ENST00000331090.11	NP_001035826.1
REC114	NM_001348772.2	c.244C>G	p.Leu82Val	missense_variant	Exon 2 of 5		NP_001335701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REC114	ENST00000331090.11	c.244C>G	p.Leu82Val	missense_variant	Exon 2 of 6	1	NM_001042367.2	ENSP00000328423.6
REC114	ENST00000560581.1	c.244C>G	p.Leu82Val	missense_variant	Exon 2 of 5	2		ENSP00000452908.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.6	L;.
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.15
Sift	Benign	0.31	T;T
Sift4G	Benign	0.28	T;T
Polyphen		1.0	D;.
Vest4		0.38
MVP		0.72
MPC		0.52
ClinPred		0.82	D
GERP RS		3.4
Varity_R		0.064
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs373897163; hg19: chr15-73766257;