13-94711613-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_007084.4(SOX21):​c.437C>A​(p.Ala146Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,076,126 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 (★).

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

SOX21
NM_007084.4 missense

Scores

5
4
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35576075).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SOX21NM_007084.4 linkc.437C>A p.Ala146Glu missense_variant Exon 1 of 1 ENST00000376945.4 NP_009015.1 Q9Y651

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SOX21ENST00000376945.4 linkc.437C>A p.Ala146Glu missense_variant Exon 1 of 1 6 NM_007084.4 ENSP00000366144.2 Q9Y651
SOX21-AS1ENST00000665450.1 linkn.132+8028G>T intron_variant Intron 1 of 3

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
0.00000279
AC:
3
AN:
1076126
Hom.:
0
Cov.:
40
AF XY:
0.00000388
AC XY:
2
AN XY:
515106
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000328
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.437C>A (p.A146E) alteration is located in exon 1 (coding exon 1) of the SOX21 gene. This alteration results from a C to A substitution at nucleotide position 437, causing the alanine (A) at amino acid position 146 to be replaced by a glutamic acid (E). 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
Pathogenic
0.82
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Uncertain
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
T
Eigen
Benign
-0.088
Eigen_PC
Benign
-0.25
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.75
T
M_CAP
Pathogenic
0.81
D
MetaRNN
Benign
0.36
T
MetaSVM
Pathogenic
0.84
D
MutationAssessor
Benign
1.8
L
PrimateAI
Pathogenic
0.93
D
PROVEAN
Benign
-0.70
N
REVEL
Uncertain
0.58
Sift
Uncertain
0.0010
D
Sift4G
Benign
0.16
T
Polyphen
0.99
D
Vest4
0.23
MutPred
0.38
Gain of solvent accessibility (P = 0.0145);
MVP
0.59
ClinPred
0.75
D
GERP RS
2.7
Varity_R
0.59
gMVP
0.87

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1720982933; hg19: chr13-95363867; API