NM_007084.4:c.437C>A

Variant names:

• chr13-94711613-G-T
• rs1720982933
• NM_007084.4:c.437C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.37
• 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 1 ACMG points.

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

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.437C>A	p.Ala146Glu	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.437C>A	p.Ala146Glu	missense	Exon 1 of 1	ENSP00000366144.2	Q9Y651
	SOX21-AS1	ENST00000665450.1		n.132+8028G>T		intron	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 21434

American (AMR) AF: 0.00 AC: 0 AN: 7302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12550

East Asian (EAS) AF: 0.00 AC: 0 AN: 22636

South Asian (SAS) AF: 0.00 AC: 0 AN: 22298

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2880

European-Non Finnish (NFE) AF: 0.00000328 AC: 3 AN: 913936

Other (OTH) AF: 0.00 AC: 0 AN: 41578

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

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	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
PhyloP100		1.4
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
Mutation Taster		=42/58	disease causing

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: rs1720982933; hg19: chr13-95363867;