Variant 12-4553033-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.607G>A(p.Glu203Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000299 in 1,604,926 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: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

RAD51AP1
NM_006479.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.32

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 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=0.13216072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51AP1	NM_006479.5 linkuse as main transcript	c.607G>A	p.Glu203Lys	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.607G>A	p.Glu203Lys	missense_variant	7/9	1	NM_006479.5	ENSP00000309479.7		Q96B01-2

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151792

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000410

AC:

AN:

244056

Hom.:

AF XY:

0.0000681

AC XY:

AN XY:

132154

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000619

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.000138

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000303

AC:

AN:

1453134

Hom.:

Cov.:

AF XY:

0.0000360

AC XY:

AN XY:

722826

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000465

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000178

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151792

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74170

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000827

Hom.:

Bravo

AF:

0.0000151

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000659

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

Mar 21, 2024

The c.658G>A (p.E220K) alteration is located in exon 8 (coding exon 8) of the RAD51AP1 gene. This alteration results from a G to A substitution at nucleotide position 658, causing the glutamic acid (E) at amino acid position 220 to be replaced by a lysine (K). 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

0.084

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.039

T;.;.

Eigen

Benign

0.049

Eigen_PC

Benign

-0.0019

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.67

T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.0

M;.;.

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.7

D;D;N

REVEL

Benign

0.10

Sift

Uncertain

0.012

D;D;D

Sift4G

Uncertain

0.051

T;T;D

Polyphen

0.70

P;B;.

Vest4

0.30

MVP

0.29

MPC

0.16

ClinPred

0.13

GERP RS

4.3

Varity_R

0.19

gMVP

0.067

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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