22-30450636-A-G

Variant names:

• chr22-30450636-A-G
• rs5753152
• NM_001376914.1:c.905-1392T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001376914.1(SEC14L3):​c.905-1392T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,056 control chromosomes in the GnomAD database, including 38,136 homozygotes. 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: 𝑓 0.70 (38136 hom., cov: 31)
• Consequence: SEC14L3 NM_001376914.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 6 publications found

Genes affected

SEC14L3 (HGNC:18655): (SEC14 like lipid binding 3) The protein encoded by this gene is highly similar to the protein encoded by the Saccharomyces cerevisiae SEC14 gene. The SEC14 protein is a phophatidylinositol transfer protein that is essential for biogenesis of Golgi-derived transport vesicles, and thus is required for the export of yeast secretory proteins from the Golgi complex. The specific function of this protein has not yet been determined. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

LOC105372991 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376914.1. 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
	SEC14L3	NM_001376914.1		c.905-1392T>C		intron	N/A	NP_001363843.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L3	ENST00000403066.5	TSL:2	c.905-1392T>C		intron	N/A	ENSP00000385941.1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106073 AN: 151938 Hom.: 38081 Cov.: 31

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.661

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.698 AC: 106188 AN: 152056 Hom.: 38136 Cov.: 31 AF XY: 0.705 AC XY: 52399 AN XY: 74328

African (AFR) AF: 0.858 AC: 35576 AN: 41488

American (AMR) AF: 0.621 AC: 9484 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2084 AN: 3468

East Asian (EAS) AF: 0.848 AC: 4388 AN: 5174

South Asian (SAS) AF: 0.817 AC: 3940 AN: 4820

European-Finnish (FIN) AF: 0.694 AC: 7332 AN: 10570

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41175 AN: 67952

Other (OTH) AF: 0.665 AC: 1404 AN: 2110

Alfa AF: 0.653 Hom.: 5538

Bravo AF: 0.694

Asia WGS AF: 0.839 AC: 2918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.39
PhyloP100		-0.033
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5753152; hg19: chr22-30846623;