9-136441147-A-G

Variant names:

• chr9-136441147-A-G
• rs1127152
• NM_014866.2:c.*608T>C

Variant summary

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

The NM_014866.2(SEC16A):​c.*608T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,994 control chromosomes in the GnomAD database, including 10,934 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 0.36 (10855 hom., cov: 33)
  • Exomes 𝑓: 0.43 (79 hom.)
• Consequence: SEC16A NM_014866.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 37 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014866.2. 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
	SEC16A	NM_014866.2	MANE Select	c.*608T>C		3_prime_UTR	Exon 32 of 32	NP_055681.1
	SEC16A	NM_001438153.1		c.*608T>C		3_prime_UTR	Exon 31 of 31	NP_001425082.1
	SEC16A	NM_001438154.1		c.*608T>C		3_prime_UTR	Exon 31 of 31	NP_001425083.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC16A	ENST00000684901.1	MANE Select	c.*608T>C		3_prime_UTR	Exon 32 of 32	ENSP00000508822.1
	SEC16A	ENST00000290037.10	TSL:1	c.*608T>C		3_prime_UTR	Exon 29 of 29	ENSP00000290037.7
	SEC16A	ENST00000453963.5	TSL:1	c.*608T>C		3_prime_UTR	Exon 26 of 26	ENSP00000403525.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55321 AN: 152022 Hom.: 10836 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.433 AC: 370 AN: 854 Hom.: 79 Cov.: 0 AF XY: 0.428 AC XY: 189 AN XY: 442

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.529 AC: 90 AN: 170

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.436 AC: 48 AN: 110

South Asian (SAS) AF: 0.261 AC: 12 AN: 46

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.432 AC: 211 AN: 488

Other (OTH) AF: 0.222 AC: 8 AN: 36

GnomAD4 genome AF: 0.364 AC: 55376 AN: 152140 Hom.: 10855 Cov.: 33 AF XY: 0.359 AC XY: 26692 AN XY: 74374

African (AFR) AF: 0.234 AC: 9716 AN: 41518

American (AMR) AF: 0.489 AC: 7481 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1571 AN: 3470

East Asian (EAS) AF: 0.217 AC: 1123 AN: 5176

South Asian (SAS) AF: 0.299 AC: 1444 AN: 4826

European-Finnish (FIN) AF: 0.318 AC: 3362 AN: 10580

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29371 AN: 67968

Other (OTH) AF: 0.392 AC: 828 AN: 2110

Alfa AF: 0.416 Hom.: 40679

Bravo AF: 0.373

Asia WGS AF: 0.299 AC: 1040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.98
DANN	Benign	0.55
PhyloP100		0.093
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: rs1127152; hg19: chr9-139335599;