Genetic Variant NM_001031748.4:c.782C>G (chr12-39682706-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001031748.4(REDIC1):c.782C>G(p.Thr261Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,612,848 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

REDIC1
NM_001031748.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0310

Variant links:

Genes affected

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

REDIC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.038787663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REDIC1	NM_001031748.4 link	c.782C>G	p.Thr261Ser	missense_variant	Exon 8 of 13	ENST00000324616.9	NP_001026918.2	Q86WS4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C12orf40	ENST00000324616.9 link	c.782C>G	p.Thr261Ser	missense_variant	Exon 8 of 13	1	NM_001031748.4	ENSP00000317671.5	Q86WS4-1
C12orf40	ENST00000405531.7 link	c.782C>G	p.Thr261Ser	missense_variant	Exon 8 of 11	1		ENSP00000383897.3	Q86WS4-2
C12orf40	ENST00000468200.2 link	n.551C>G		non_coding_transcript_exon_variant	Exon 7 of 19	1		ENSP00000473371.1	Q86WS4-3

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

249008

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135114

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.0000171

AC:

AN:

1460790

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726724

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.000118

AC:

AN:

152058

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.000242

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.000196

ESP6500AA

AF:

0.000816

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000331

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.782C>G (p.T261S) alteration is located in exon 8 (coding exon 8) of the C12orf40 gene. This alteration results from a C to G substitution at nucleotide position 782, causing the threonine (T) at amino acid position 261 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

0.13

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.6

DANN

Benign

0.88

DEOGEN2

Benign

0.0043

.;T

Eigen

Benign

-0.90

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.31

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.044

Sift

Benign

0.068

T;T

Sift4G

Benign

0.078

T;T

Polyphen

0.39

.;B

Vest4

0.12

MutPred

0.15

Gain of disorder (P = 0.0413);Gain of disorder (P = 0.0413);

MVP

0.088

MPC

0.033

ClinPred

0.014

GERP RS

-2.9

Varity_R

0.060

gMVP

0.049

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