13-94711493-G-A

Variant names:

• chr13-94711493-G-A
• rs770331980
• NM_007084.4:c.557C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_007084.4(SOX21):​c.557C>T​(p.Ser186Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,031,412 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S186W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: SOX21 NM_007084.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.38
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26815385).
• BS2: High AC in GnomAdExome4 at 110 AD gene.

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.557C>T	p.Ser186Leu	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.557C>T	p.Ser186Leu	missense	Exon 1 of 1	ENSP00000366144.2	Q9Y651
	SOX21-AS1	ENST00000665450.1		n.132+7908G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000693 AC: 1 AN: 144370 Hom.: 0 Cov.: 30

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: 0.0000153

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000124 AC: 110 AN: 887042 Hom.: 0 Cov.: 40 AF XY: 0.000120 AC XY: 50 AN XY: 415236

African (AFR) AF: 0.00 AC: 0 AN: 17636

American (AMR) AF: 0.00 AC: 0 AN: 2848

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5602

East Asian (EAS) AF: 0.00 AC: 0 AN: 6878

South Asian (SAS) AF: 0.00 AC: 0 AN: 19610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2584

European-Non Finnish (NFE) AF: 0.000137 AC: 108 AN: 786564

Other (OTH) AF: 0.0000685 AC: 2 AN: 29212

GnomAD4 genome AF: 0.00000693 AC: 1 AN: 144370 Hom.: 0 Cov.: 30 AF XY: 0.0000143 AC XY: 1 AN XY: 70116

African (AFR) AF: 0.00 AC: 0 AN: 40152

American (AMR) AF: 0.00 AC: 0 AN: 14628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3352

East Asian (EAS) AF: 0.00 AC: 0 AN: 4924

South Asian (SAS) AF: 0.00 AC: 0 AN: 4704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000153 AC: 1 AN: 65254

Other (OTH) AF: 0.00 AC: 0 AN: 1996

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.25
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.097	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T
M_CAP	Pathogenic	0.84	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	-0.049	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.4
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.56	N
REVEL	Uncertain	0.40
Sift	Benign	0.073	T
Sift4G	Benign	0.33	T
Polyphen		0.58	P
Vest4		0.28
MutPred		0.23		Loss of phosphorylation at S186 (P = 0.0205)
MVP		0.70
ClinPred		0.48	T
GERP RS		2.1
Varity_R		0.11
gMVP		0.55
Mutation Taster		=76/24	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: rs770331980; hg19: chr13-95363747;