rs757660

Positions:

• chr22-30397148-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012429.5(SEC14L2):​c.32G>A​(p.Arg11Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,544,374 control chromosomes in the GnomAD database, including 80,072 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.35 (9442 hom., cov: 31)
  • Exomes 𝑓: 0.32 (70630 hom.)
• Consequence: SEC14L2 NM_012429.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013599396).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC14L2	NM_012429.5	c.32G>A	p.Arg11Lys	missense_variant	1/12	ENST00000615189.5
SEC14L2	NM_033382.3	c.32G>A	p.Arg11Lys	missense_variant	1/11
SEC14L2	NM_001204204.3	c.32G>A	p.Arg11Lys	missense_variant	1/10
SEC14L2	NM_001291932.2	c.-55G>A		5_prime_UTR_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC14L2	ENST00000615189.5	c.32G>A	p.Arg11Lys	missense_variant	1/12	1	NM_012429.5	P1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52675 AN: 151420 Hom.: 9428 Cov.: 31

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.317

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.329

GnomAD3 exomes AF: 0.337 AC: 49563 AN: 147020 Hom.: 8638 AF XY: 0.337 AC XY: 26379 AN XY: 78256

Gnomad AFR exome AF: 0.397

Gnomad AMR exome AF: 0.352

Gnomad ASJ exome AF: 0.240

Gnomad EAS exome AF: 0.373

Gnomad SAS exome AF: 0.383

Gnomad FIN exome AF: 0.400

Gnomad NFE exome AF: 0.296

Gnomad OTH exome AF: 0.307

GnomAD4 exome AF: 0.315 AC: 439203 AN: 1392836 Hom.: 70630 Cov.: 36 AF XY: 0.317 AC XY: 217877 AN XY: 686992

Gnomad4 AFR exome AF: 0.412

Gnomad4 AMR exome AF: 0.357

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.379

Gnomad4 SAS exome AF: 0.387

Gnomad4 FIN exome AF: 0.403

Gnomad4 NFE exome AF: 0.301

Gnomad4 OTH exome AF: 0.325

GnomAD4 genome AF: 0.348 AC: 52731 AN: 151538 Hom.: 9442 Cov.: 31 AF XY: 0.354 AC XY: 26246 AN XY: 74076

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.337

Alfa AF: 0.309 Hom.: 14814

Bravo AF: 0.342

TwinsUK AF: 0.307 AC: 1139

ALSPAC AF: 0.296 AC: 1139

ESP6500AA AF: 0.354 AC: 1467

ESP6500EA AF: 0.249 AC: 2010

ExAC AF: 0.186 AC: 15365

Asia WGS AF: 0.413 AC: 1433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.96
DEOGEN2	Benign	0.013	T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0078	N
LIST_S2	Benign	0.015	T;T;T
MetaRNN	Benign	0.0014	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.6	N;N;N
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.42	T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.020
ClinPred		0.0026	T
GERP RS		0.65
Varity_R		0.13
gMVP		0.35

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: rs757660; hg19: chr22-30793137; COSMIC: COSV57240484; COSMIC: COSV57240484;