chr22-30421381-A-G

Variant names:

• chr22-30421381-A-G
• rs2299829
• NM_012429.5:c.1082-896A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012429.5(SEC14L2):​c.1082-896A>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SEC14L2 NM_012429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663
• Publications: 6 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]

ENSG00000249590 (HGNC:):

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]

RNU6-564P (HGNC:47527): (RNA, U6 small nuclear 564, pseudogene)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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.1082-896A>G		intron	N/A	NP_036561.1
	SEC14L2	NM_001291932.2		c.920-896A>G		intron	N/A	NP_001278861.1
	SEC14L2	NM_001204204.3		c.833-896A>G		intron	N/A	NP_001191133.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L2	ENST00000615189.5	TSL:1 MANE Select	c.1082-896A>G		intron	N/A	ENSP00000478755.1
	ENSG00000249590	ENST00000439838.5	TSL:2	c.583+4978A>G		intron	N/A	ENSP00000415178.1
	SEC14L2	ENST00000619483.4	TSL:1	n.1177-896A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.78
PhyloP100		-0.66
PromoterAI		0.031	Neutral

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: rs2299829; hg19: chr22-30817370;