Variant 12-4543897-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000352618.9(RAD51AP1):c.202A>C(p.Lys68Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0039 in 1,599,814 control chromosomes in the GnomAD database, including 201 homozygotes. 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 Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.022 ( 97 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 104 hom. )

Consequence

RAD51AP1
ENST00000352618.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.72

Variant links:

Genes affected

RAD51AP1 (HGNC:16956): (RAD51 associated protein 1) Enables nucleic acid binding activity. Involved in DNA repair; cellular response to ionizing radiation; and positive regulation of DNA recombination. Located in chromatin and nucleus. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

RAD51AP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018510222).

BP6

Variant 12-4543897-A-C is Benign according to our data. Variant chr12-4543897-A-C is described in ClinVar as [Benign]. Clinvar id is 768505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51AP1	NM_006479.5 linkuse as main transcript	c.202A>C	p.Lys68Gln	missense_variant	3/9	ENST00000352618.9	NP_006470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51AP1	ENST00000352618.9 linkuse as main transcript	c.202A>C	p.Lys68Gln	missense_variant	3/9	1	NM_006479.5	ENSP00000309479	P1	Q96B01-2

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3308

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0751

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.00567

AC:

1368

AN:

241266

Hom.:

AF XY:

0.00418

AC XY:

545

AN XY:

130498

show subpopulations

Gnomad AFR exome

AF:

0.0763

Gnomad AMR exome

AF:

0.00376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000141

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000127

Gnomad OTH exome

AF:

0.00239

GnomAD4 exome

AF:

0.00203

AC:

2933

AN:

1447642

Hom.:

104

Cov.:

AF XY:

0.00172

AC XY:

1239

AN XY:

720398

show subpopulations

Gnomad4 AFR exome

AF:

0.0747

Gnomad4 AMR exome

AF:

0.00394

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000143

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000489

Gnomad4 OTH exome

AF:

0.00423

GnomAD4 genome

AF:

0.0217

AC:

3308

AN:

152172

Hom.:

Cov.:

AF XY:

0.0217

AC XY:

1616

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0749

Gnomad4 AMR

AF:

0.00981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.00425

Hom.:

Bravo

AF:

0.0253

ESP6500AA

AF:

0.0722

AC:

318

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00690

AC:

837

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0084

T;.;.

Eigen

Benign

0.046

Eigen_PC

Benign

0.021

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.85

T;D;D

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.0

M;M;.

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.070

Sift

Uncertain

0.010

D;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.19

B;D;.

Vest4

0.16

MVP

0.32

MPC

0.49

ClinPred

0.037

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.073

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