chr22-30397148-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012429.5(SEC14L2):​c.32G>T​(p.Arg11Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SEC14L2 NM_012429.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09093651).

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>T	p.Arg11Met	missense	Exon 1 of 12	NP_036561.1
	SEC14L2	NM_001291932.2		c.-55G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001278861.1
	SEC14L2	NM_033382.3		c.32G>T	p.Arg11Met	missense	Exon 1 of 11	NP_203740.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L2	ENST00000615189.5	TSL:1 MANE Select	c.32G>T	p.Arg11Met	missense	Exon 1 of 12	ENSP00000478755.1
	SEC14L2	ENST00000405717.7	TSL:1	c.32G>T	p.Arg11Met	missense	Exon 1 of 11	ENSP00000385186.3
	SEC14L2	ENST00000619483.4	TSL:1	n.154G>T		non_coding_transcript_exon	Exon 1 of 11

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1393910 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 687540

African (AFR) AF: 0.00 AC: 0 AN: 31050

American (AMR) AF: 0.00 AC: 0 AN: 35398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24884

East Asian (EAS) AF: 0.00 AC: 0 AN: 35202

South Asian (SAS) AF: 0.00 AC: 0 AN: 78854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077076

Other (OTH) AF: 0.00 AC: 0 AN: 57794

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.32
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.027
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.059	T
Polyphen		0.0050	B
Vest4		0.21
MutPred		0.48		Loss of MoRF binding (P = 0.007)
MVP		0.22
ClinPred		0.51	D
GERP RS		0.65
PromoterAI		0.0067	Neutral
Varity_R		0.17
gMVP		0.50
Mutation Taster		=81/19	polymorphism

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;