chr22-30409292-A-T

Position:

• chr22-30409292-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_012429.5(SEC14L2):​c.519+10A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SEC14L2 NM_012429.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.15

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 (BayesDel_noAF=-0.78).
• BP6: Variant 22-30409292-A-T is Benign according to our data. Variant chr22-30409292-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 761094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC14L2	NM_012429.5	c.519+10A>T		intron_variant		ENST00000615189.5
SEC14L2	NM_001204204.3	c.270+10A>T		intron_variant
SEC14L2	NM_001291932.2	c.357+10A>T		intron_variant
SEC14L2	NM_033382.3	c.519+10A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC14L2	ENST00000615189.5	c.519+10A>T		intron_variant		1	NM_012429.5	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 29 AN: 142914 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.000253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000717

Gnomad SAS AF: 0.00153

Gnomad FIN AF: 0.000220

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000765

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00112 AC: 929 AN: 833110 Hom.: 0 Cov.: 29 AF XY: 0.00100 AC XY: 428 AN XY: 427328

Gnomad4 AFR exome AF: 0.000886

Gnomad4 AMR exome AF: 0.000338

Gnomad4 ASJ exome AF: 0.00105

Gnomad4 EAS exome AF: 0.000600

Gnomad4 SAS exome AF: 0.000199

Gnomad4 FIN exome AF: 0.000218

Gnomad4 NFE exome AF: 0.00137

Gnomad4 OTH exome AF: 0.00129

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000210 AC: 30 AN: 143068 Hom.: 0 Cov.: 32 AF XY: 0.000172 AC XY: 12 AN XY: 69572

Gnomad4 AFR AF: 0.000278

Gnomad4 AMR AF: 0.000209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000717

Gnomad4 SAS AF: 0.00153

Gnomad4 FIN AF: 0.000220

Gnomad4 NFE AF: 0.0000765

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.3
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1601778622; hg19: chr22-30805281;