8-47291081-G-T

Position:

• chr8-47291081-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080394.4(SPIDR):​c.305G>T​(p.Ser102Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPIDR NM_001080394.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.46

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]

ACMG classification

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=0.15295869).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPIDR	NM_001080394.4	c.305G>T	p.Ser102Ile	missense_variant	4/20	ENST00000297423.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPIDR	ENST00000297423.9	c.305G>T	p.Ser102Ile	missense_variant	4/20	1	NM_001080394.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2023

The c.305G>T (p.S102I) alteration is located in exon 4 (coding exon 4) of the SPIDR gene. This alteration results from a G to T substitution at nucleotide position 305, causing the serine (S) at amino acid position 102 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	Uncertain	0.34
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;.;.
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.099
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.2	M;.;.
MutationTaster	Benign	0.79	D;D;D
PROVEAN	Uncertain	-2.5	D;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.25
MutPred		0.21		Loss of phosphorylation at S102 (P = 0.0122);.;.;
MVP		0.21
MPC		0.052
ClinPred		0.96	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.39

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

Other links and lift over

dbSNP: rs1231880244; hg19: chr8-48203670;