9-136441809-G-A

Position:

• chr9-136441809-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014866.2(SEC16A):​c.7020C>T​(p.Ser2340=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00624 in 1,613,116 control chromosomes in the GnomAD database, including 291 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (168 hom., cov: 33)
  • Exomes 𝑓: 0.0044 (123 hom.)
• Consequence: SEC16A NM_014866.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.50

Genes affected

SEC16A (HGNC:29006): (SEC16 homolog A, endoplasmic reticulum export factor) This gene encodes a protein that forms part of the Sec16 complex. This protein has a role in protein transport from the endoplasmic reticulum (ER) to the Golgi and mediates COPII vesicle formation at the transitional ER. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Feb 2013]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-136441809-G-A is Benign according to our data. Variant chr9-136441809-G-A is described in ClinVar as [Benign]. Clinvar id is 780840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.5 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.075 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC16A	NM_014866.2	c.7020C>T	p.Ser2340=	synonymous_variant	32/32	ENST00000684901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC16A	ENST00000684901.1	c.7020C>T	p.Ser2340=	synonymous_variant	32/32		NM_014866.2	A2

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3624 AN: 152202 Hom.: 168 Cov.: 33

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00298

Gnomad OTH AF: 0.0163

GnomAD3 exomes AF: 0.00729 AC: 1807 AN: 247964 Hom.: 51 AF XY: 0.00588 AC XY: 793 AN XY: 134912

Gnomad AFR exome AF: 0.0796

Gnomad AMR exome AF: 0.00461

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00182

Gnomad NFE exome AF: 0.00314

Gnomad OTH exome AF: 0.00482

GnomAD4 exome AF: 0.00440 AC: 6432 AN: 1460796 Hom.: 123 Cov.: 30 AF XY: 0.00404 AC XY: 2938 AN XY: 726676

Gnomad4 AFR exome AF: 0.0834

Gnomad4 AMR exome AF: 0.00485

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000243

Gnomad4 FIN exome AF: 0.00163

Gnomad4 NFE exome AF: 0.00256

Gnomad4 OTH exome AF: 0.00714

GnomAD4 genome AF: 0.0238 AC: 3628 AN: 152320 Hom.: 168 Cov.: 33 AF XY: 0.0230 AC XY: 1711 AN XY: 74484

Gnomad4 AFR AF: 0.0772

Gnomad4 AMR AF: 0.0100

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00298

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0116 Hom.: 34

Bravo AF: 0.0269

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00185

EpiControl AF: 0.00219

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 19, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.45
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs45568431; hg19: chr9-139336261;