Variant 12-4553054-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_006479.5(RAD51AP1):c.628A>T(p.Ser210Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000271 in 1,606,938 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

RAD51AP1
NM_006479.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.50

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:

RAD51AP1 (HGNC:):

RAD51AP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009019256).

BP6

Variant 12-4553054-A-T is Benign according to our data. Variant chr12-4553054-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 707896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51AP1	NM_006479.5 linkuse as main transcript	c.628A>T	p.Ser210Cys	missense_variant	7/9	ENST00000352618.9	NP_006470.1	Q96B01-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51AP1	ENST00000352618.9 linkuse as main transcript	c.628A>T	p.Ser210Cys	missense_variant	7/9	1	NM_006479.5	ENSP00000309479.7		Q96B01-2

Frequencies

GnomAD3 genomes

AF:

0.00157

AC:

239

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00543

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

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:

0.00

GnomAD3 exomes

AF:

0.000380

AC:

AN:

244656

Hom.:

AF XY:

0.000226

AC XY:

AN XY:

132542

show subpopulations

Gnomad AFR exome

AF:

0.00506

Gnomad AMR exome

AF:

0.000429

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:

0.000135

AC:

197

AN:

1454582

Hom.:

Cov.:

AF XY:

0.000112

AC XY:

AN XY:

723604

show subpopulations

Gnomad4 AFR exome

AF:

0.00507

Gnomad4 AMR exome

AF:

0.000439

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:

0.00

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.00156

AC:

238

AN:

152356

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00539

Gnomad4 AMR

AF:

0.000915

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:

0.00

Alfa

AF:

0.000979

Hom.:

Bravo

AF:

0.00191

ESP6500AA

AF:

0.00454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000519

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.072

T;.;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.0090

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.6

M;.;.

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Benign

0.084

Sift

Uncertain

0.017

D;D;D

Sift4G

Uncertain

0.039

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.26

MVP

0.33

MPC

0.48

ClinPred

0.079

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.15

gMVP

0.028

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