15-73443216-C-T

Variant names:

• chr15-73443216-C-T
• rs1274587754
• NM_001042367.2:c.31C>T

Variant summary

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

The NM_001042367.2(REC114):​c.31C>T​(p.Leu11Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: REC114 NM_001042367.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135

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=0.08544266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REC114	NM_001042367.2	c.31C>T	p.Leu11Phe	missense_variant	Exon 1 of 6	ENST00000331090.11	NP_001035826.1
REC114	NM_001348772.2	c.31C>T	p.Leu11Phe	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	c.31C>T	p.Leu11Phe	missense_variant	Exon 1 of 6	1	NM_001042367.2	ENSP00000328423.6
REC114	ENST00000560581.1	c.31C>T	p.Leu11Phe	missense_variant	Exon 1 of 5	2		ENSP00000452908.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152218 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74368

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.1
DANN	Benign	0.93
DEOGEN2	Benign	0.027	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.43	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.085	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.022
Sift	Benign	0.075	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.087	B;.
Vest4		0.18
MutPred		0.22		Gain of methylation at K6 (P = 0.1023);Gain of methylation at K6 (P = 0.1023);
MVP		0.072
MPC		0.20
ClinPred		0.13	T
GERP RS		-0.85
Varity_R		0.051
gMVP		0.15

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: rs1274587754; hg19: chr15-73735557;