Variant chr8-47291071-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080394.4(SPIDR):c.295A>G(p.Ile99Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,613,430 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

SPIDR
NM_001080394.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03778124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPIDR	NM_001080394.4 linkuse as main transcript	c.295A>G	p.Ile99Val	missense_variant	4/20	ENST00000297423.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPIDR	ENST00000297423.9 linkuse as main transcript	c.295A>G	p.Ile99Val	missense_variant	4/20	1	NM_001080394.4	P1	Q14159-1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00143

GnomAD4 exome

AF:

0.000235

AC:

343

AN:

1461082

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

166

AN XY:

726812

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000985

Gnomad4 ASJ exome

AF:

0.00525

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000243

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00142

Bravo

AF:

0.000408

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

Apr 17, 2023

The c.295A>G (p.I99V) alteration is located in exon 4 (coding exon 4) of the SPIDR gene. This alteration results from a A to G substitution at nucleotide position 295, causing the isoleucine (I) at amino acid position 99 to be replaced by a valine (V). 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

0.20

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.13

T;.;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.62

T;T;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.038

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

-0.59

N;N;N

REVEL

Benign

0.099

Sift

Benign

0.034

D;D;D

Sift4G

Uncertain

0.040

D;D;D

Polyphen

0.059

B;.;.

Vest4

0.31

MutPred

0.12

Gain of glycosylation at S104 (P = 0.126);.;.;

MVP

0.014

MPC

0.096

ClinPred

0.53

GERP RS

-0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.024

gMVP

0.11

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