chr13-94711745-C-G

Variant names:

• chr13-94711745-C-G
• rs2138618384
• NM_007084.4:c.305G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007084.4(SOX21):​c.305G>C​(p.Gly102Ala) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SOX21 NM_007084.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.57
• Publications: 0 publications found

Genes affected

SOX21 (HGNC:11197): (SRY-box transcription factor 21) SRY-related HMG-box (SOX) genes encode a family of DNA-binding proteins containing a 79-amino acid HMG (high mobility group) domain that shares at least 50% sequence identity with the DNA-binding HMG box of the SRY protein (MIM 480000). SOX proteins are divided into 6 subgroups based on sequence similarity within and outside of the HMG domain. For additional background information on SOX genes, see SOX1 (MIM 602148).[supplied by OMIM, Apr 2004]

SOX21-AS1 (HGNC:39807): (SOX21 antisense divergent transcript 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24684504).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007084.4. 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
	SOX21	NM_007084.4	MANE Select	c.305G>C	p.Gly102Ala	missense	Exon 1 of 1	NP_009015.1	Q9Y651

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX21	ENST00000376945.4	TSL:6 MANE Select	c.305G>C	p.Gly102Ala	missense	Exon 1 of 1	ENSP00000366144.2	Q9Y651
	SOX21-AS1	ENST00000665450.1		n.132+8160C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.48	T
M_CAP	Pathogenic	0.99	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.11	D
MutationAssessor	Benign	1.0	L
PhyloP100		3.6
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.28
Sift	Benign	0.16	T
Sift4G	Uncertain	0.014	D
Polyphen		0.0	B
Vest4		0.12
MutPred		0.28		Gain of helix (P = 0.0854)
MVP		0.60
ClinPred		0.10	T
GERP RS		2.2
Varity_R		0.14
gMVP		0.54
Mutation Taster		=93/7	polymorphism

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: rs2138618384; hg19: chr13-95363999;