chr22-30397148-G-A

Variant names:

• chr22-30397148-G-A
• rs757660
• NM_012429.5:c.32G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012429.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L2	NM_012429.5	MANE Select	c.32G>A	p.Arg11Lys	missense	Exon 1 of 12	NP_036561.1
	SEC14L2	NM_033382.3		c.32G>A	p.Arg11Lys	missense	Exon 1 of 11	NP_203740.1
	SEC14L2	NM_001204204.3		c.32G>A	p.Arg11Lys	missense	Exon 1 of 10	NP_001191133.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L2	ENST00000615189.5	TSL:1 MANE Select	c.32G>A	p.Arg11Lys	missense	Exon 1 of 12	ENSP00000478755.1
	SEC14L2	ENST00000405717.7	TSL:1	c.32G>A	p.Arg11Lys	missense	Exon 1 of 11	ENSP00000385186.3
	SEC14L2	ENST00000619483.4	TSL:1	n.154G>A		non_coding_transcript_exon	Exon 1 of 11

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

GnomAD2 exomes AF: 0.337 AC: 49563 AN: 147020 AF XY: 0.337

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 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

African (AFR) AF: 0.412 AC: 12778 AN: 31018

American (AMR) AF: 0.357 AC: 12602 AN: 35338

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 5887 AN: 24858

East Asian (EAS) AF: 0.379 AC: 13320 AN: 35156

South Asian (SAS) AF: 0.387 AC: 30474 AN: 78752

European-Finnish (FIN) AF: 0.403 AC: 19221 AN: 47736

Middle Eastern (MID) AF: 0.410 AC: 2312 AN: 5640

European-Non Finnish (NFE) AF: 0.301 AC: 323844 AN: 1076594

Other (OTH) AF: 0.325 AC: 18765 AN: 57744

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

African (AFR) AF: 0.407 AC: 16822 AN: 41296

American (AMR) AF: 0.347 AC: 5295 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 830 AN: 3468

East Asian (EAS) AF: 0.371 AC: 1887 AN: 5084

South Asian (SAS) AF: 0.379 AC: 1819 AN: 4804

European-Finnish (FIN) AF: 0.402 AC: 4220 AN: 10510

Middle Eastern (MID) AF: 0.314 AC: 91 AN: 290

European-Non Finnish (NFE) AF: 0.305 AC: 20679 AN: 67824

Other (OTH) AF: 0.337 AC: 707 AN: 2098

Alfa AF: 0.314 Hom.: 22328

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 v4.9

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
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.6	N
PhyloP100		0.32
PrimateAI	Benign	0.42	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.080
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.020
ClinPred		0.0026	T
GERP RS		0.65
PromoterAI		0.081	Neutral
Varity_R		0.13
gMVP		0.35
Mutation Taster		=100/0	polymorphism (auto)

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