Variant 20-326475-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006943.4(SOX12):c.551G>C(p.Arg184Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,396,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

SOX12
NM_006943.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.325

Variant links:

Genes affected

SOX12 (HGNC:11198): (SRY-box transcription factor 12) Members of the SOX family of transcription factors are characterized by the presence of a DNA-binding high mobility group (HMG) domain, homologous to the HMG box of sex-determining region Y (SRY). Forming a subgroup of the HMG domain superfamily, SOX proteins have been implicated in cell fate decisions in a diverse range of developmental processes. SOX transcription factors have diverse tissue-specific expression patterns during early development and have been proposed to act as target-specific transcription factors and/or as chromatin structure regulatory elements. The protein encoded by this gene was identified as a SOX family member based on conserved domains, and its expression in various tissues suggests a role in both differentiation and maintenance of several cell types. [provided by RefSeq, Jan 2013]

SOX12 links:

NRSN2-AS1 (HGNC:51222): (NRSN2 antisense RNA 1)

NRSN2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32259956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX12	NM_006943.4 linkuse as main transcript	c.551G>C	p.Arg184Pro	missense_variant	1/1	ENST00000342665.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SOX12	ENST00000342665.5 linkuse as main transcript	c.551G>C	p.Arg184Pro	missense_variant	1/1		NM_006943.4	P1
NRSN2-AS1	ENST00000662580.1 linkuse as main transcript	n.221-3910C>G		intron_variant, non_coding_transcript_variant
NRSN2-AS1	ENST00000442637.2 linkuse as main transcript	n.126-3910C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

8.04e-7

AC:

AN:

1244034

Hom.:

Cov.:

AF XY:

0.00000165

AC XY:

AN XY:

606282

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000344

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

AF:

0.0000132

AC:

AN:

152034

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 05, 2022

The c.551G>C (p.R184P) alteration is located in exon 1 (coding exon 1) of the SOX12 gene. This alteration results from a G to C substitution at nucleotide position 551, causing the arginine (R) at amino acid position 184 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.081

Eigen

Benign

0.14

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.32

MetaSVM

Uncertain

0.59

MutationAssessor

Benign

0.34

MutationTaster

Benign

0.86

N;N

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.40

Sift

Benign

0.17

Sift4G

Uncertain

0.024

Polyphen

1.0

Vest4

0.075

MutPred

0.31

Loss of MoRF binding (P = 0.0021);

MVP

0.85

ClinPred

0.73

GERP RS

3.6

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.8

Varity_R

0.36

gMVP

0.35

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over