Variant 15-73473916-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001042367.2(REC114):c.244C>A(p.Leu82Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000425 in 1,412,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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: 0.0000042 ( 0 hom. )

Consequence

REC114
NM_001042367.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

Variant links:

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]

REC114 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.22555915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REC114	NM_001042367.2 linkuse as main transcript	c.244C>A	p.Leu82Ile	missense_variant	2/6	ENST00000331090.11	NP_001035826.1
REC114	NM_001348772.2 linkuse as main transcript	c.244C>A	p.Leu82Ile	missense_variant	2/5		NP_001335701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REC114	ENST00000331090.11 linkuse as main transcript	c.244C>A	p.Leu82Ile	missense_variant	2/6	1	NM_001042367.2	ENSP00000328423.6		Q7Z4M0
REC114	ENST00000560581.1 linkuse as main transcript	c.244C>A	p.Leu82Ile	missense_variant	2/5	2		ENSP00000452908.1		H0YKR2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000243

AC:

AN:

205664

Hom.:

AF XY:

0.00

AC XY:

AN XY:

109844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000169

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000425

AC:

AN:

1412596

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

700908

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000147

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000167

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2024

The c.244C>A (p.L82I) alteration is located in exon 2 (coding exon 2) of the REC114 gene. This alteration results from a C to A substitution at nucleotide position 244, causing the leucine (L) at amino acid position 82 to be replaced by an isoleucine (I). 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

0.24

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

T;T

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0092

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.3

M;.

PROVEAN

Benign

-0.74

N;N

REVEL

Benign

0.16

Sift

Benign

0.075

T;T

Sift4G

Uncertain

0.051

T;T

Polyphen

1.0

D;.

Vest4

0.46

MutPred

0.27

Gain of catalytic residue at L82 (P = 0.0063);Gain of catalytic residue at L82 (P = 0.0063);

MVP

0.71

MPC

0.55

ClinPred

0.46

GERP RS

3.4

Varity_R

0.063

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over