chr22-30459710-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174975.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L3	NM_174975.5	MANE Select	c.*311G>A		3_prime_UTR	Exon 12 of 12	NP_777635.1	Q9UDX4-1
	SEC14L3	NM_001257379.2		c.*311G>A		3_prime_UTR	Exon 13 of 13	NP_001244308.1	Q9UDX4-2
	SEC14L3	NM_001257382.2		c.*311G>A		3_prime_UTR	Exon 13 of 13	NP_001244311.1	Q9UDX4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L3	ENST00000215812.9	TSL:1 MANE Select	c.*311G>A		3_prime_UTR	Exon 12 of 12	ENSP00000215812.5	Q9UDX4-1
	SEC14L3	ENST00000401751.5	TSL:1	c.*311G>A		3_prime_UTR	Exon 13 of 13	ENSP00000383896.1	Q9UDX4-2
	SEC14L3	ENST00000402286.5	TSL:1	c.*311G>A		3_prime_UTR	Exon 14 of 14	ENSP00000385004.1	Q9UDX4-3

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

African (AFR) AF: 0.222 AC: 4247 AN: 19104

American (AMR) AF: 0.225 AC: 1316 AN: 5860

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 2307 AN: 7568

East Asian (EAS) AF: 0.307 AC: 2775 AN: 9032

South Asian (SAS) AF: 0.221 AC: 4463 AN: 20156

European-Finnish (FIN) AF: 0.279 AC: 811 AN: 2902

Middle Eastern (MID) AF: 0.246 AC: 466 AN: 1898

European-Non Finnish (NFE) AF: 0.279 AC: 224211 AN: 802532

Other (OTH) AF: 0.278 AC: 8704 AN: 31342

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

African (AFR) AF: 0.222 AC: 9225 AN: 41492

American (AMR) AF: 0.211 AC: 3218 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1073 AN: 3472

East Asian (EAS) AF: 0.311 AC: 1608 AN: 5178

South Asian (SAS) AF: 0.218 AC: 1051 AN: 4820

European-Finnish (FIN) AF: 0.267 AC: 2824 AN: 10570

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18848 AN: 67988

Other (OTH) AF: 0.251 AC: 530 AN: 2114

Alfa AF: 0.267 Hom.: 24081

Bravo AF: 0.253

Asia WGS AF: 0.254 AC: 882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.41
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

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: rs5753158; hg19: chr22-30855697;