Variant 8-47284040-G-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.202G>A(p.Glu68Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000968 in 1,610,952 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00088 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00098 ( 3 hom. )

Consequence

SPIDR
NM_001080394.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.34

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=0.05897352).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPIDR	NM_001080394.4 linkuse as main transcript	c.202G>A	p.Glu68Lys	missense_variant	3/20	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.202G>A	p.Glu68Lys	missense_variant	3/20	1	NM_001080394.4	ENSP00000297423.4		Q14159-1

Frequencies

GnomAD3 genomes

AF:

0.000881

AC:

134

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00331

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00135

Gnomad OTH

AF:

0.00144

GnomAD4 exome

AF:

0.000978

AC:

1426

AN:

1458754

Hom.:

Cov.:

AF XY:

0.000904

AC XY:

656

AN XY:

725764

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00364

Gnomad4 NFE exome

AF:

0.00103

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.000880

AC:

134

AN:

152198

Hom.:

Cov.:

AF XY:

0.000968

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00331

Gnomad4 NFE

AF:

0.00135

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000569

Hom.:

Bravo

AF:

0.000635

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

Feb 10, 2022

The c.202G>A (p.E68K) alteration is located in exon 3 (coding exon 3) of the SPIDR gene. This alteration results from a G to A substitution at nucleotide position 202, causing the glutamic acid (E) at amino acid position 68 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

0.073

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

T;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.056

FATHMM_MKL

Benign

0.34

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.0026

MetaRNN

Benign

0.059

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.2

M;.

PROVEAN

Benign

-0.99

N;N

REVEL

Benign

0.075

Sift

Benign

0.14

T;D

Sift4G

Benign

0.16

T;D

Polyphen

0.45

B;.

Vest4

0.14

MutPred

0.16

Gain of ubiquitination at E68 (P = 0.0037);.;

MVP

0.076

MPC

0.10

ClinPred

0.81

GERP RS

2.9

Varity_R

0.031

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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