rs13279327

Variant names:

• chr8-47529822-T-C
• rs13279327
• NM_001080394.4:c.1098-65989T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080394.4(SPIDR):​c.1098-65989T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,148 control chromosomes in the GnomAD database, including 6,261 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6261 hom., cov: 33)
• Consequence: SPIDR NM_001080394.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• 46 XX gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• ovarian dysgenesis 9

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: NO_KNOWN Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPIDR	NM_001080394.4	c.1098-65989T>C		intron_variant	Intron 8 of 19	ENST00000297423.9	NP_001073863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPIDR	ENST00000297423.9	c.1098-65989T>C		intron_variant	Intron 8 of 19	1	NM_001080394.4	ENSP00000297423.4

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42523 AN: 152028 Hom.: 6258 Cov.: 33

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.286

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.280 AC: 42546 AN: 152148 Hom.: 6261 Cov.: 33 AF XY: 0.282 AC XY: 20969 AN XY: 74368

African (AFR) AF: 0.269 AC: 11174 AN: 41506

American (AMR) AF: 0.201 AC: 3078 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1431 AN: 3466

East Asian (EAS) AF: 0.192 AC: 992 AN: 5180

South Asian (SAS) AF: 0.447 AC: 2158 AN: 4830

European-Finnish (FIN) AF: 0.306 AC: 3238 AN: 10584

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19474 AN: 67978

Other (OTH) AF: 0.284 AC: 600 AN: 2112

Alfa AF: 0.292 Hom.: 12207

Asia WGS AF: 0.312 AC: 1085 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.97
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13279327; hg19: chr8-48442384;