3-137765112-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004189.4(SOX14):​c.328C>A​(p.Leu110Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SOX14
NM_004189.4 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.70
Variant links:
Genes affected
SOX14 (HGNC:11193): (SRY-box transcription factor 14) This intronless gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. Mutations in this gene are suggested to be responsible for the limb defects associated with blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) and Mobius syndrome. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SOX14NM_004189.4 linkc.328C>A p.Leu110Met missense_variant Exon 1 of 1 ENST00000306087.3 NP_004180.1 O95416

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SOX14ENST00000306087.3 linkc.328C>A p.Leu110Met missense_variant Exon 1 of 1 6 NM_004189.4 ENSP00000305343.1 O95416

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.328C>A (p.L110M) alteration is located in exon 1 (coding exon 1) of the SOX14 gene. This alteration results from a C to A substitution at nucleotide position 328, causing the leucine (L) at amino acid position 110 to be replaced by a methionine (M). 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
Benign
0.075
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.065
T
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.77
T
M_CAP
Pathogenic
0.31
D
MetaRNN
Uncertain
0.47
T
MetaSVM
Pathogenic
0.92
D
MutationAssessor
Benign
2.0
M
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-0.49
N
REVEL
Uncertain
0.58
Sift
Benign
0.033
D
Sift4G
Benign
0.14
T
Polyphen
1.0
D
Vest4
0.29
MutPred
0.24
Loss of catalytic residue at L110 (P = 0.1335);
MVP
0.73
MPC
1.4
ClinPred
0.89
D
GERP RS
3.8
Varity_R
0.46
gMVP
0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-137483954; API