NM_033127.4:c.2798A>T

Variant names:

• chr1-177933239-T-A
• rs201106348
• NM_033127.4:c.2798A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033127.4(SEC16B):​c.2798A>T​(p.Asp933Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000286 in 1,589,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D933G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: SEC16B NM_033127.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33
• Publications: 0 publications found

Genes affected

SEC16B (HGNC:30301): (SEC16 homolog B, endoplasmic reticulum export factor) SEC16B is a mammalian homolog of S. cerevisiae Sec16 that is required for organization of transitional endoplasmic reticulum (ER) sites and protein export (Bhattacharyya and Glick, 2007 [PubMed 17192411]).[supplied by OMIM, Jun 2009]

CRYZL2P-SEC16B (HGNC:53757): (CRYZL2P-SEC16B readthrough) This locus represents naturally occurring read-through transcription between the neighboring CRYZL2P (crystallin zeta like 2 pseudogene) and SEC16B (SEC16 homolog B, endoplasmic reticulum export factor) genes on chromosome 1. The readthrough transcript encodes a protein that shares sequence identity with the downstream gene product. [provided by RefSeq, Oct 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007985592).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033127.4. 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
	SEC16B	NM_033127.4	MANE Select	c.2798A>T	p.Asp933Val	missense	Exon 22 of 26	NP_149118.2	Q96JE7-1
	SEC16B	NM_001390834.1		c.2801A>T	p.Asp934Val	missense	Exon 22 of 26	NP_001377763.1
	SEC16B	NM_001390835.1		c.2801A>T	p.Asp934Val	missense	Exon 22 of 26	NP_001377764.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC16B	ENST00000308284.11	TSL:1 MANE Select	c.2798A>T	p.Asp933Val	missense	Exon 22 of 26	ENSP00000308339.6	Q96JE7-1
	SEC16B	ENST00000528461.5	TSL:1	n.*1785A>T		non_coding_transcript_exon	Exon 21 of 25	ENSP00000475522.1	U3KQ39
	SEC16B	ENST00000528461.5	TSL:1	n.*1785A>T		3_prime_UTR	Exon 21 of 25	ENSP00000475522.1	U3KQ39

Frequencies

GnomAD3 genomes AF: 0.00150 AC: 226 AN: 150890 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00513

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000789

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.000967

GnomAD2 exomes AF: 0.000380 AC: 81 AN: 213302 AF XY: 0.000306

Gnomad AFR exome AF: 0.00582

Gnomad AMR exome AF: 0.000259

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000156 AC: 224 AN: 1438548 Hom.: 0 Cov.: 31 AF XY: 0.000142 AC XY: 101 AN XY: 712984

African (AFR) AF: 0.00525 AC: 173 AN: 32940

American (AMR) AF: 0.000336 AC: 14 AN: 41654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25626

East Asian (EAS) AF: 0.0000259 AC: 1 AN: 38666

South Asian (SAS) AF: 0.0000365 AC: 3 AN: 82186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51850

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5738

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1100338

Other (OTH) AF: 0.000521 AC: 31 AN: 59550

GnomAD4 genome AF: 0.00153 AC: 231 AN: 151008 Hom.: 0 Cov.: 32 AF XY: 0.00146 AC XY: 108 AN XY: 73746

African (AFR) AF: 0.00524 AC: 215 AN: 41066

American (AMR) AF: 0.000788 AC: 12 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5074

South Asian (SAS) AF: 0.00 AC: 0 AN: 4708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67724

Other (OTH) AF: 0.000957 AC: 2 AN: 2090

Alfa AF: 0.000128 Hom.: 0

Bravo AF: 0.00170

ESP6500AA AF: 0.00631 AC: 25

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000356 AC: 43

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.0080	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.070
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.016	D
Polyphen		0.22	B
Vest4		0.28
MVP		0.16
MPC		0.29
ClinPred		0.059	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.28
Mutation Taster		=98/2	polymorphism

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: rs201106348; hg19: chr1-177902374; COSMIC: COSV106098174; COSMIC: COSV106098174;