1-204123202-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_005686.3(SOX13):c.1225A>G(p.Met409Val) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000082 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SOX13 NM_005686.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.460

Genes affected

SOX13 (HGNC:11192): (SRY-box transcription factor 13) This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. It has also been determined to be a type-1 diabetes autoantigen, also known as islet cell antibody 12. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06086144).
• BP6: Variant 1-204123202-A-G is Benign according to our data. Variant chr1-204123202-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2266994.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX13	NM_005686.3	c.1225A>G	p.Met409Val	missense_variant	11/14	ENST00000367204.6
SOX13	XM_047435006.1	c.1225A>G	p.Met409Val	missense_variant	11/14
SOX13	XM_005245623.4	c.1222A>G	p.Met408Val	missense_variant	11/14
SOX13	XM_047435007.1	c.1222A>G	p.Met408Val	missense_variant	11/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX13	ENST00000367204.6	c.1225A>G	p.Met409Val	missense_variant	11/14	1	NM_005686.3	P1
SOX13	ENST00000618875.4	c.1225A>G	p.Met409Val	missense_variant	10/13	1		P1
SOX13	ENST00000272193.10	n.1092A>G		non_coding_transcript_exon_variant	8/11	2
SOX13	ENST00000525258.1	n.669A>G		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000822 AC: 12 AN: 1460316 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 726582

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000990

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
Cadd	Benign	0.63
Dann	Benign	0.53
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.29	N
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.061	T;T
MetaSVM	Uncertain	-0.092	T
MutationAssessor	Benign	1.9	L;L
MutationTaster	Benign	0.80	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.23
Sift	Benign	0.46	T;.
Sift4G	Benign	0.81	T;T
Polyphen		0.0	B;B
Vest4		0.19
MutPred		0.18		Gain of catalytic residue at M409 (P = 0.032);Gain of catalytic residue at M409 (P = 0.032);
MVP		0.53
MPC		0.31
ClinPred		0.045	T
GERP RS		-6.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.070
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: chr1-204092330;