Variant chr1-15935970-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong

The NM_015001.3(SPEN):c.9730A>T(p.Thr3244Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T3244P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000031 ( 0 hom., cov: 9)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SPEN
NM_015001.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.451

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SPEN. . Gene score misZ 2.8932 (greater than the threshold 3.09). Trascript score misZ 5.0985 (greater than threshold 3.09). GenCC has associacion of gene with complex neurodevelopmental disorder, Radio-Tartaglia syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.028619349).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPEN	NM_015001.3 linkuse as main transcript	c.9730A>T	p.Thr3244Ser	missense_variant	11/15	ENST00000375759.8	NP_055816.2	Q96T58

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SPEN	ENST00000375759.8 linkuse as main transcript	c.9730A>T	p.Thr3244Ser	missense_variant	11/15	1	NM_015001.3	ENSP00000364912.3	Q96T58
SPEN	ENST00000704274.1 linkuse as main transcript	c.5326A>T	p.Thr1776Ser	missense_variant	1/4			ENSP00000515812.1	A0A994J7B7
SPEN	ENST00000438066.2 linkuse as main transcript	n.*10581A>T		non_coding_transcript_exon_variant	11/15	3		ENSP00000388021.2	F6WRY4
SPEN	ENST00000438066.2 linkuse as main transcript	n.*10581A>T		3_prime_UTR_variant	11/15	3		ENSP00000388021.2	F6WRY4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

65240

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000659

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

693718

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

351408

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000307

AC:

AN:

65240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

30938

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000659

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.058

DANN

Benign

0.17

DEOGEN2

Benign

0.086

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.27

M_CAP

Benign

0.0050

MetaRNN

Benign

0.029

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-2.0

PrimateAI

Benign

0.43

PROVEAN

Benign

0.55

REVEL

Benign

0.018

Sift

Benign

0.27

Sift4G

Benign

0.97

Polyphen

0.0

Vest4

0.088

MutPred

0.19

Loss of methylation at K3240 (P = 0.1492);

MVP

0.043

MPC

0.21

ClinPred

0.063

GERP RS

-0.36

Varity_R

0.032

gMVP

0.051

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over