NM_138402.6:c.523+3759C>T

Variant names:

• chr2-230365456-C-T
• rs6712333
• NM_138402.6:c.523+3759C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138402.6(SP140L):​c.523+3759C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 151,720 control chromosomes in the GnomAD database, including 7,643 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 0.27 (7643 hom., cov: 32)
• Consequence: SP140L NM_138402.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

Genes affected

SP140L (HGNC:25105): (SP140 nuclear body protein like) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nuclear body. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP140L	NM_138402.6	c.523+3759C>T		intron_variant	Intron 5 of 18	ENST00000415673.7	NP_612411.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP140L	ENST00000415673.7	c.523+3759C>T		intron_variant	Intron 5 of 18	5	NM_138402.6	ENSP00000397911.2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40518 AN: 151602 Hom.: 7610 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.268 AC: 40607 AN: 151720 Hom.: 7643 Cov.: 32 AF XY: 0.275 AC XY: 20355 AN XY: 74140

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.253

Alfa AF: 0.164 Hom.: 1390

Bravo AF: 0.292

Asia WGS AF: 0.425 AC: 1477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.56

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: rs6712333; hg19: chr2-231230171;