3-137765337-C-G

Variant names:

• chr3-137765337-C-G
• NM_004189.4:c.553C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004189.4(SOX14):​c.553C>G​(p.Gln185Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SOX14 NM_004189.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.12

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19299272).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX14	NM_004189.4	c.553C>G	p.Gln185Glu	missense_variant	Exon 1 of 1	ENST00000306087.3	NP_004180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX14	ENST00000306087.3	c.553C>G	p.Gln185Glu	missense_variant	Exon 1 of 1	6	NM_004189.4	ENSP00000305343.1

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

Submissions by phenotype

not specified Uncertain:1

Oct 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.553C>G (p.Q185E) alteration is located in exon 1 (coding exon 1) of the SOX14 gene. This alteration results from a C to G substitution at nucleotide position 553, causing the glutamine (Q) at amino acid position 185 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	Benign	0.19
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.018
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.19	T
MetaSVM	Uncertain	0.32	D
MutationAssessor	Benign	1.2	L
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.44	N
REVEL	Uncertain	0.41
Sift	Benign	0.11	T
Sift4G	Benign	0.31	T
Polyphen		0.0080	B
Vest4		0.48
MutPred		0.17		Loss of stability (P = 0.1698);
MVP		0.81
MPC		0.99
ClinPred		0.70	D
GERP RS		4.7
Varity_R		0.35
gMVP		0.81

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: chr3-137484179;