22-30459710-C-T

Variant names:

• chr22-30459710-C-T
• rs5753158
• NM_174975.5:c.*311G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174975.5(SEC14L3):​c.*311G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,052,516 control chromosomes in the GnomAD database, including 39,994 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 0.25 (5017 hom., cov: 32)
  • Exomes 𝑓: 0.28 (34977 hom.)
• Consequence: SEC14L3 NM_174975.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC14L3	NM_174975.5	c.*311G>A		3_prime_UTR_variant	Exon 12 of 12	ENST00000215812.9	NP_777635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC14L3	ENST00000215812	c.*311G>A		3_prime_UTR_variant	Exon 12 of 12	1	NM_174975.5	ENSP00000215812.5

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38721 AN: 152004 Hom.: 5021 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.277 AC: 249300 AN: 900394 Hom.: 34977 Cov.: 30 AF XY: 0.277 AC XY: 115968 AN XY: 419142

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.305

Gnomad4 EAS exome AF: 0.307

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.255 AC: 38733 AN: 152122 Hom.: 5017 Cov.: 32 AF XY: 0.251 AC XY: 18678 AN XY: 74370

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.251

Alfa AF: 0.271 Hom.: 11567

Bravo AF: 0.253

Asia WGS AF: 0.254 AC: 882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs5753158; hg19: chr22-30855697;