17-77190913-C-G

Position:

• chr17-77190913-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The ENST00000436233.9(SEC14L1):​c.174C>G​(p.Arg58=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00255 in 1,614,222 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (12 hom.)
• Consequence: SEC14L1 ENST00000436233.9 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.64

Genes affected

SEC14L1 (HGNC:10698): (SEC14 like lipid binding 1) The protein encoded by this gene belongs to the SEC14 cytosolic factor family. It has similarity to yeast SEC14 and to Japanese flying squid RALBP which suggests a possible role of the gene product in an intracellular transport system. Multiple alternatively spliced transcript variants have been found for this gene; some variants represent read-through transcripts that include exons from the upstream gene C17orf86. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 17-77190913-C-G is Benign according to our data. Variant chr17-77190913-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 730749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC14L1	NM_001143998.2	c.174C>G	p.Arg58=	synonymous_variant	4/17	ENST00000436233.9	NP_001137470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC14L1	ENST00000436233.9	c.174C>G	p.Arg58=	synonymous_variant	4/17	1	NM_001143998.2	ENSP00000390392

Frequencies

GnomAD3 genomes AF: 0.00181 AC: 275 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00319

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00158 AC: 398 AN: 251470 Hom.: 2 AF XY: 0.00158 AC XY: 215 AN XY: 135906

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.000983

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000490

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.00283

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.00262 AC: 3836 AN: 1461880 Hom.: 12 Cov.: 32 AF XY: 0.00254 AC XY: 1844 AN XY: 727242

Gnomad4 AFR exome AF: 0.000597

Gnomad4 AMR exome AF: 0.000783

Gnomad4 ASJ exome AF: 0.000612

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000429

Gnomad4 FIN exome AF: 0.000374

Gnomad4 NFE exome AF: 0.00320

Gnomad4 OTH exome AF: 0.00252

GnomAD4 genome AF: 0.00181 AC: 275 AN: 152342 Hom.: 0 Cov.: 32 AF XY: 0.00152 AC XY: 113 AN XY: 74502

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00319

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00244 Hom.: 1

Bravo AF: 0.00192

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00300

EpiControl AF: 0.00279

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	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	SEC14L1: BP4 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs144815495; hg19: chr17-75186995;