chr12-39682706-C-T

Variant names:

• chr12-39682706-C-T
• rs201570915
• NM_001031748.4:c.782C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001031748.4(REDIC1):​c.782C>T​(p.Thr261Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: REDIC1 NM_001031748.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310

Genes affected

REDIC1 (HGNC:26846): (regulator of DNA class I crossover intermediates 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037648886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REDIC1	NM_001031748.4	c.782C>T	p.Thr261Ile	missense_variant	Exon 8 of 13	ENST00000324616.9	NP_001026918.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C12orf40	ENST00000324616.9	c.782C>T	p.Thr261Ile	missense_variant	Exon 8 of 13	1	NM_001031748.4	ENSP00000317671.5
C12orf40	ENST00000405531.7	c.782C>T	p.Thr261Ile	missense_variant	Exon 8 of 11	1		ENSP00000383897.3
C12orf40	ENST00000468200.2	n.551C>T		non_coding_transcript_exon_variant	Exon 7 of 19	1		ENSP00000473371.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000803 AC: 2 AN: 249008 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135114

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.0000556

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: 0.00000137 AC: 2 AN: 1460790 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726724

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000253

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.: 33

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.1
DANN	Benign	0.60
DEOGEN2	Benign	0.0030	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0065	N
LIST_S2	Benign	0.38	T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.038	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.42	N;N
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.058
Sift	Benign	0.53	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.017	.;B
Vest4		0.048
MutPred		0.30		Loss of phosphorylation at T261 (P = 0.0262);Loss of phosphorylation at T261 (P = 0.0262);
MVP		0.055
MPC		0.018
ClinPred		0.016	T
GERP RS		-2.9
Varity_R		0.040
gMVP		0.079

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

Other links and lift over

dbSNP: rs201570915; hg19: chr12-40076508;