Variant 12-4556493-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006479.5(RAD51AP1):c.862G>A(p.Val288Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,246 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

RAD51AP1
NM_006479.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.926

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:

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ACMG classification

Classification made for transcript

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=0.12043068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51AP1	NM_006479.5 linkuse as main transcript	c.862G>A	p.Val288Ile	missense_variant	8/9	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.862G>A	p.Val288Ile	missense_variant	8/9	1	NM_006479.5	ENSP00000309479.7		Q96B01-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251100

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461246

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The c.913G>A (p.V305I) alteration is located in exon 9 (coding exon 9) of the RAD51AP1 gene. This alteration results from a G to A substitution at nucleotide position 913, causing the valine (V) at amino acid position 305 to be replaced by an isoleucine (I). 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

0.10

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0029

T;.

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.48

N;N

REVEL

Benign

0.088

Sift

Benign

0.25

T;T

Sift4G

Benign

0.48

T;T

Polyphen

1.0

D;B

Vest4

0.13

MutPred

0.29

Gain of catalytic residue at P307 (P = 0);.;

MVP

0.44

MPC

0.092

ClinPred

0.55

GERP RS

4.8

Varity_R

0.063

gMVP

0.092

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