chr20-326570-G-C

Position:

• chr20-326570-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006943.4(SOX12):​c.646G>C​(p.Ala216Pro) variant causes a missense 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SOX12 NM_006943.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.839

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]

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1769054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX12	NM_006943.4	c.646G>C	p.Ala216Pro	missense_variant	1/1	ENST00000342665.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX12	ENST00000342665.5	c.646G>C	p.Ala216Pro	missense_variant	1/1		NM_006943.4	P1
NRSN2-AS1	ENST00000662580.1	n.221-4005C>G		intron_variant, non_coding_transcript_variant
NRSN2-AS1	ENST00000442637.2	n.126-4005C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.646G>C (p.A216P) 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 646, causing the alanine (A) at amino acid position 216 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	Benign	0.073
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	15
DANN	Benign	0.80
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.47	T
M_CAP	Pathogenic	0.99	D
MetaRNN	Benign	0.18	T
MetaSVM	Uncertain	0.24	D
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	0.93	N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	1.0	N
REVEL	Benign	0.27
Sift	Benign	0.33	T
Sift4G	Benign	0.26	T
Vest4		0.30
MutPred		0.31		Gain of loop (P = 0.0013);
MVP		0.68
ClinPred		0.18	T
GERP RS		1.9
Varity_R		0.12
gMVP		0.11

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: chr20-307214;