chr15-73443244-A-T

Position:

• chr15-73443244-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001042367.2(REC114):​c.59A>T​(p.Glu20Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: REC114 NM_001042367.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29570496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REC114	NM_001042367.2	c.59A>T	p.Glu20Val	missense_variant	1/6	ENST00000331090.11	NP_001035826.1
REC114	NM_001348772.2	c.59A>T	p.Glu20Val	missense_variant	1/5		NP_001335701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REC114	ENST00000331090.11	c.59A>T	p.Glu20Val	missense_variant	1/6	1	NM_001042367.2	ENSP00000328423.6
REC114	ENST00000560581.1	c.59A>T	p.Glu20Val	missense_variant	1/5	2		ENSP00000452908.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2023

The c.59A>T (p.E20V) alteration is located in exon 1 (coding exon 1) of the REC114 gene. This alteration results from a A to T substitution at nucleotide position 59, causing the glutamic acid (E) at amino acid position 20 to be replaced by a valine (V). 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	0.21
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N;.
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.033
Sift	Benign	0.14	T;T
Sift4G	Benign	0.23	T;T
Polyphen		0.72	P;.
Vest4		0.37
MutPred		0.24		Loss of disorder (P = 0.0244);Loss of disorder (P = 0.0244);
MVP		0.44
MPC		0.33
ClinPred		0.42	T
GERP RS		3.5
Varity_R		0.16
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-73735585;