Genetic Variant SEC16B:p.Thr943Asn (chr1-177932802-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_033127.4(SEC16B):c.2828C>A(p.Thr943Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,610,124 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 (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SEC16B
NM_033127.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.456

Publications

0 publications found

Variant links:

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]

SEC16B links:

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]

CRYZL2P-SEC16B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.017018318).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEC16B	NM_033127.4	MANE Select	c.2828C>A	p.Thr943Asn	missense	Exon 23 of 26	NP_149118.2	Q96JE7-1
SEC16B	NM_001390834.1		c.2834C>A	p.Thr945Asn	missense	Exon 23 of 26	NP_001377763.1
SEC16B	NM_001390835.1		c.2834C>A	p.Thr945Asn	missense	Exon 23 of 26	NP_001377764.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEC16B	ENST00000308284.11	TSL:1 MANE Select	c.2828C>A	p.Thr943Asn	missense	Exon 23 of 26	ENSP00000308339.6	Q96JE7-1
SEC16B	ENST00000528461.5	TSL:1	n.*1815C>A		non_coding_transcript_exon	Exon 22 of 25	ENSP00000475522.1	U3KQ39
SEC16B	ENST00000528461.5	TSL:1	n.*1815C>A		3_prime_UTR	Exon 22 of 25	ENSP00000475522.1	U3KQ39

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000376

AC:

AN:

239376

AF XY:

0.0000386

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000173

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1457896

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

724700

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26018

East Asian (EAS)

AF:

0.00

AC:

AN:

39628

South Asian (SAS)

AF:

0.000200

AC:

AN:

85160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52824

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110558

Other (OTH)

AF:

0.0000166

AC:

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68048

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000331

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.3

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.0050

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.27

M_CAP

Benign

0.0026

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

PhyloP100

0.46

PrimateAI

Benign

0.33

PROVEAN

Benign

0.23

REVEL

Benign

0.11

Sift

Benign

0.18

Sift4G

Benign

0.40

Polyphen

0.0010

Vest4

0.055

MutPred

0.14

Loss of phosphorylation at T943 (P = 0.0016)

MVP

0.040

MPC

0.042

ClinPred

0.034

GERP RS

-0.073

Varity_R

0.047

gMVP

0.093

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over