Variant 15-73443249-C-T 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.64C>T(p.Pro22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,573,342 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

REC114
NM_001042367.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59

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=0.13304761).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REC114	NM_001042367.2 link	c.64C>T	p.Pro22Ser	missense_variant	Exon 1 of 6	ENST00000331090.11	NP_001035826.1
REC114	NM_001348772.2 link	c.64C>T	p.Pro22Ser	missense_variant	Exon 1 of 5		NP_001335701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REC114	ENST00000331090.11 link	c.64C>T	p.Pro22Ser	missense_variant	Exon 1 of 6	1	NM_001042367.2	ENSP00000328423.6		Q7Z4M0
REC114	ENST00000560581.1 link	c.64C>T	p.Pro22Ser	missense_variant	Exon 1 of 5	2		ENSP00000452908.1		H0YKR2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000882

AC:

AN:

181462

Hom.:

AF XY:

0.0000819

AC XY:

AN XY:

97640

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000112

Gnomad ASJ exome

AF:

0.000337

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.000206

GnomAD4 exome

AF:

0.000104

AC:

148

AN:

1421004

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

703136

show subpopulations

Gnomad4 AFR exome

AF:

0.0000615

Gnomad4 AMR exome

AF:

0.000131

Gnomad4 ASJ exome

AF:

0.000511

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.0000679

GnomAD4 genome

AF:

0.000112

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000137

Hom.:

Bravo

AF:

0.000110

ExAC

AF:

0.0000420

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

Nov 25, 2024

The c.64C>T (p.P22S) alteration is located in exon 1 (coding exon 1) of the REC114 gene. This alteration results from a C to T substitution at nucleotide position 64, causing the proline (P) at amino acid position 22 to be replaced by a serine (S). 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

0.25

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.083

T;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.

PROVEAN

Uncertain

-4.0

D;D

REVEL

Benign

0.016

Sift

Benign

0.12

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.29

B;.

Vest4

0.41

MVP

0.46

MPC

0.29

ClinPred

0.10

GERP RS

2.5

Varity_R

0.10

gMVP

0.37

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

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