rs10514971

Variant names:

• chr17-49661184-C-T
• rs10514971
• NM_001007228.2:c.-67+16749G>A

Variant summary

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

The NM_001007228.2(SPOP):​c.-67+16749G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,084 control chromosomes in the GnomAD database, including 2,121 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 0.15 (2121 hom., cov: 31)
• Consequence: SPOP NM_001007228.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393
• Publications: 8 publications found

Genes affected

SPOP (HGNC:11254): (speckle type BTB/POZ protein) This gene encodes a protein that may modulate the transcriptional repression activities of death-associated protein 6 (DAXX), which interacts with histone deacetylase, core histones, and other histone-associated proteins. In mouse, the encoded protein binds to the putative leucine zipper domain of macroH2A1.2, a variant H2A histone that is enriched on inactivated X chromosomes. The BTB/POZ domain of this protein has been shown in other proteins to mediate transcriptional repression and to interact with components of histone deacetylase co-repressor complexes. Alternative splicing of this gene results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

SPOP Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• neurodevelopmental disorder with microcephaly and dysmorphic facies

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• neurodevelopmental disorder with relative macrocephaly and with or without cardiac or endocrine anomalies

  Inheritance: AD Classification: STRONG Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007228.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPOP	NM_001007228.2	MANE Select	c.-67+16749G>A		intron	N/A	NP_001007229.1	O43791
	SPOP	NM_001007226.1		c.-67+6843G>A		intron	N/A	NP_001007227.1	O43791
	SPOP	NM_001007227.1		c.-67+6843G>A		intron	N/A	NP_001007228.1	O43791

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPOP	ENST00000504102.6	TSL:1 MANE Select	c.-67+16749G>A		intron	N/A	ENSP00000425905.1	O43791
	SPOP	ENST00000393328.6	TSL:1	c.-67+14711G>A		intron	N/A	ENSP00000377001.2	O43791
	SPOP	ENST00000347630.6	TSL:5	c.-118+16749G>A		intron	N/A	ENSP00000240327.2	O43791

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22275 AN: 151966 Hom.: 2119 Cov.: 31

Gnomad AFR AF: 0.0388

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0659

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.146 AC: 22278 AN: 152084 Hom.: 2121 Cov.: 31 AF XY: 0.145 AC XY: 10783 AN XY: 74340

African (AFR) AF: 0.0388 AC: 1609 AN: 41502

American (AMR) AF: 0.181 AC: 2764 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 423 AN: 3466

East Asian (EAS) AF: 0.0662 AC: 343 AN: 5178

South Asian (SAS) AF: 0.181 AC: 876 AN: 4830

European-Finnish (FIN) AF: 0.170 AC: 1788 AN: 10532

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14042 AN: 67988

Other (OTH) AF: 0.146 AC: 308 AN: 2114

Alfa AF: 0.185 Hom.: 4022

Bravo AF: 0.141

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.2
DANN	Benign	0.52
PhyloP100		-0.39
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: rs10514971; hg19: chr17-47738546;