Variant chr8-47260965-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001080394.4(SPIDR):c.7C>A(p.Arg3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,229,532 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00089 ( 3 hom. )

Consequence

SPIDR
NM_001080394.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.97

Variant links:

Genes affected

SPIDR (HGNC:28971): (scaffold protein involved in DNA repair) Involved in several processes, including cellular response to camptothecin; cellular response to hydroxyurea; and regulation of double-strand break repair. Located in nuclear chromosome and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SPIDR links:

SPIDR (HGNC:):

SPIDR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028096437).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPIDR	NM_001080394.4 linkuse as main transcript	c.7C>A	p.Arg3Ser	missense_variant	1/20	ENST00000297423.9	NP_001073863.1	Q14159-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPIDR	ENST00000297423.9 linkuse as main transcript	c.7C>A	p.Arg3Ser	missense_variant	1/20	1	NM_001080394.4	ENSP00000297423.4		Q14159-1

Frequencies

GnomAD3 genomes

AF:

0.00262

AC:

398

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00657

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000948

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00102

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00704

AC:

AN:

142

Hom.:

AF XY:

0.00

AC XY:

AN XY:

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:

0.00

Gnomad NFE exome

AF:

0.0116

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000891

AC:

960

AN:

1077422

Hom.:

Cov.:

AF XY:

0.000906

AC XY:

462

AN XY:

509768

show subpopulations

Gnomad4 AFR exome

AF:

0.00561

Gnomad4 AMR exome

AF:

0.00439

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000945

Gnomad4 NFE exome

AF:

0.000755

Gnomad4 OTH exome

AF:

0.00190

GnomAD4 genome

AF:

0.00261

AC:

397

AN:

152110

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

188

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00652

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000948

Gnomad4 NFE

AF:

0.00102

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.000696

Hom.:

Bravo

AF:

0.00332

ExAC

AF:

0.000364

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

Jan 26, 2022

The c.7C>A (p.R3S) alteration is located in exon 1 (coding exon 1) of the SPIDR gene. This alteration results from a C to A substitution at nucleotide position 7, causing the arginine (R) at amino acid position 3 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

0.24

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.47

DANN

Benign

0.63

DEOGEN2

Benign

0.0037

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PROVEAN

Benign

-0.11

REVEL

Benign

0.024

Sift

Benign

0.53

Sift4G

Pathogenic

0.0

Polyphen

0.33

Vest4

0.21

MVP

0.014

MPC

0.16

ClinPred

0.094

GERP RS

-5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.058

gMVP

0.29

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