rs1319561958

Variant names:

• chr1-15848139-G-A
• NM_015001.3:c.72G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-15848139-G-A
• chr1-15848139-G-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015001.3(SPEN):​c.72G>A​(p.Glu24Glu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPEN NM_015001.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45

Genes affected

SPEN (HGNC:17575): (spen family transcriptional repressor) This gene encodes a hormone inducible transcriptional repressor. Repression of transcription by this gene product can occur through interactions with other repressors, by the recruitment of proteins involved in histone deacetylation, or through sequestration of transcriptional activators. The product of this gene contains a carboxy-terminal domain that permits binding to other corepressor proteins. This domain also permits interaction with members of the NuRD complex, a nucleosome remodeling protein complex that contains deacetylase activity. In addition, this repressor contains several RNA recognition motifs that confer binding to a steroid receptor RNA coactivator; this binding can modulate the activity of both liganded and nonliganded steroid receptors. [provided by RefSeq, Jul 2008]

SPEN-AS1 (HGNC:55937): (SPEN antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=2.45 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPEN	NM_015001.3	c.72G>A	p.Glu24Glu	synonymous_variant	Exon 1 of 15	ENST00000375759.8	NP_055816.2
SPEN-AS1	NR_024279.1	n.9C>T		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPEN	ENST00000375759.8	c.72G>A	p.Glu24Glu	synonymous_variant	Exon 1 of 15	1	NM_015001.3	ENSP00000364912.3
SPEN	ENST00000673875.1	c.-220+11254G>A		intron_variant	Intron 1 of 11			ENSP00000501122.1
SPEN-AS1	ENST00000317122.2	n.9C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2
SPEN	ENST00000438066.2	n.72G>A		non_coding_transcript_exon_variant	Exon 1 of 15	3		ENSP00000388021.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1342970 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 666100

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Uncertain	0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-16174634;