chr14-24173385-C-T

Position:

• chr14-24173385-C-T

Variant summary

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

The NM_001048205.2(REC8):​c.436C>T​(p.Leu146Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: REC8 NM_001048205.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.86

Genes affected

REC8 (HGNC:16879): (REC8 meiotic recombination protein) This gene encodes a member of the kleisin family of SMC (structural maintenance of chromosome) protein partners. The protein localizes to the axial elements of chromosomes during meiosis in both oocytes and spermatocytes. In the mouse, the homologous protein is a key component of the meiotic cohesion complex, which regulates sister chromatid cohesion and recombination between homologous chromosomes. Multiple alternatively spliced variants, encoding the same protein, have been found for this gene. [provided by RefSeq, Jul 2008]

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=0.24267828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REC8	NM_001048205.2	c.436C>T	p.Leu146Phe	missense_variant	5/19	ENST00000611366.5	NP_001041670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REC8	ENST00000611366.5	c.436C>T	p.Leu146Phe	missense_variant	5/19	1	NM_001048205.2	ENSP00000482439.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Nov 07, 2022

The c.436C>T (p.L146F) alteration is located in exon 5 (coding exon 5) of the REC8 gene. This alteration results from a C to T substitution at nucleotide position 436, causing the leucine (L) at amino acid position 146 to be replaced by a phenylalanine (F). 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	0.30
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.23	T;T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Benign	0.74	D
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.1	M;M;.
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.6	.;.;D
Sift	Uncertain	0.023	.;.;D
Sift4G	Uncertain	0.031	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.31
MutPred		0.21		Loss of catalytic residue at L146 (P = 0.0607);Loss of catalytic residue at L146 (P = 0.0607);.;
MVP		0.46
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.18
gMVP		0.69

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: chr14-24642594;