15-73556335-G-C

Variant names:

• chr15-73556335-G-C
• rs200297290
• NM_001042367.2:c.580G>C

Variant summary

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

The NM_001042367.2(REC114):​c.580G>C​(p.Val194Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: REC114 NM_001042367.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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 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=0.059719324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REC114	NM_001042367.2	c.580G>C	p.Val194Leu	missense_variant	Exon 5 of 6	ENST00000331090.11	NP_001035826.1
REC114	NM_001348772.2	c.496G>C	p.Val166Leu	missense_variant	Exon 4 of 5		NP_001335701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REC114	ENST00000331090.11	c.580G>C	p.Val194Leu	missense_variant	Exon 5 of 6	1	NM_001042367.2	ENSP00000328423.6
REC114	ENST00000560581.1	c.496G>C	p.Val166Leu	missense_variant	Exon 4 of 5	2		ENSP00000452908.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248630 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134826

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000889

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461496 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727014

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.10
DANN	Benign	0.53
DEOGEN2	Benign	0.011	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.
PROVEAN	Benign	-0.70	N;N
REVEL	Benign	0.034
Sift	Benign	0.39	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.017	B;.
Vest4		0.12
MutPred		0.15		Loss of sheet (P = 0.0315);.;
MVP		0.040
MPC		0.11
ClinPred		0.027	T
GERP RS		-3.7
Varity_R		0.033
gMVP		0.098

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs200297290; hg19: chr15-73848676;