22-30397150-C-G

Variant names:

• chr22-30397150-C-G
• rs772340735
• NM_012429.5:c.34C>G

Variant summary

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

The NM_012429.5(SEC14L2):​c.34C>G​(p.Gln12Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,545,080 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: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: SEC14L2 NM_012429.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96

Genes affected

SEC14L2 (HGNC:10699): (SEC14 like lipid binding 2) This gene encodes a cytosolic protein which belongs to a family of lipid-binding proteins including Sec14p, alpha-tocopherol transfer protein, and cellular retinol-binding protein. The encoded protein stimulates squalene monooxygenase which is a downstream enzyme in the cholesterol biosynthetic pathway. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Oct 2008]

RNF215 (HGNC:33434): (ring finger protein 215) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in Golgi to vacuole transport; protein targeting to vacuole; and ubiquitin-dependent protein catabolic process. Predicted to be integral component of membrane. Predicted to be part of Golgi transport complex. Predicted to be active in endosome; membrane; and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

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=0.23167425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC14L2	NM_012429.5	c.34C>G	p.Gln12Glu	missense_variant	Exon 1 of 12	ENST00000615189.5	NP_036561.1
SEC14L2	NM_033382.3	c.34C>G	p.Gln12Glu	missense_variant	Exon 1 of 11		NP_203740.1
SEC14L2	NM_001204204.3	c.34C>G	p.Gln12Glu	missense_variant	Exon 1 of 10		NP_001191133.1
SEC14L2	NM_001291932.2	c.-53C>G		5_prime_UTR_variant	Exon 1 of 11		NP_001278861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC14L2	ENST00000615189.5	c.34C>G	p.Gln12Glu	missense_variant	Exon 1 of 12	1	NM_012429.5	ENSP00000478755.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152084 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000681 AC: 10 AN: 146736 Hom.: 0 AF XY: 0.0000513 AC XY: 4 AN XY: 78026

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000329

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000183

Gnomad OTH exome AF: 0.000240

GnomAD4 exome AF: 0.0000101 AC: 14 AN: 1392996 Hom.: 0 Cov.: 33 AF XY: 0.00000873 AC XY: 6 AN XY: 687008

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000312

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: 0.00000279

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152084 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74312

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000718

ExAC AF: 0.0000112 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.34C>G (p.Q12E) alteration is located in exon 1 (coding exon 1) of the SEC14L2 gene. This alteration results from a C to G substitution at nucleotide position 34, causing the glutamine (Q) at amino acid position 12 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	0.27
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Pathogenic	3.2	M;M;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.9	.;N;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	.;D;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		0.81	P;P;.
Vest4		0.41
MutPred		0.57		Loss of MoRF binding (P = 0.0295);Loss of MoRF binding (P = 0.0295);Loss of MoRF binding (P = 0.0295);
MVP		0.32
ClinPred		0.62	D
GERP RS		4.2
Varity_R		0.74
gMVP		0.80

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

Other links and lift over

dbSNP: rs772340735; hg19: chr22-30793139;