13-94711245-G-C

Variant names:

• chr13-94711245-G-C
• rs760114683
• NM_007084.4:c.805C>G

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.805C>G​(p.Pro269Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P269S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SOX21 NM_007084.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35
• 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=0.25477165).

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.805C>G	p.Pro269Ala	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.805C>G	p.Pro269Ala	missense	Exon 1 of 1	ENSP00000366144.2	Q9Y651
	SOX21-AS1	ENST00000665450.1		n.132+7660G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1215984 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 594518

African (AFR) AF: 0.00 AC: 0 AN: 24634

American (AMR) AF: 0.00 AC: 0 AN: 13426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18136

East Asian (EAS) AF: 0.00 AC: 0 AN: 28242

South Asian (SAS) AF: 0.00 AC: 0 AN: 50540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3572

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 998300

Other (OTH) AF: 0.00 AC: 0 AN: 49458

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152116 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74318

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Benign	0.81
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.15
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	0.97	L
PhyloP100		2.4
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.42
Sift	Benign	0.64	T
Sift4G	Benign	1.0	T
Polyphen		0.77	P
Vest4		0.47
MutPred		0.32		Loss of loop (P = 0.0073)
MVP		0.74
ClinPred		0.44	T
GERP RS		3.9
Varity_R		0.13
gMVP		0.57
Mutation Taster		=82/18	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: rs760114683; hg19: chr13-95363499;