dbSNP rs752373222: SEC16B:p.Thr943Ile (chr1-177932802-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033127.4(SEC16B):c.2828C>T(p.Thr943Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,896 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T943N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SEC16B
NM_033127.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031255662).

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>T	p.Thr943Ile	missense	Exon 23 of 26	NP_149118.2	Q96JE7-1
SEC16B	NM_001390834.1		c.2834C>T	p.Thr945Ile	missense	Exon 23 of 26	NP_001377763.1
SEC16B	NM_001390835.1		c.2834C>T	p.Thr945Ile	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>T	p.Thr943Ile	missense	Exon 23 of 26	ENSP00000308339.6	Q96JE7-1
SEC16B	ENST00000528461.5	TSL:1	n.*1815C>T		non_coding_transcript_exon	Exon 22 of 25	ENSP00000475522.1	U3KQ39
SEC16B	ENST00000528461.5	TSL:1	n.*1815C>T		3_prime_UTR	Exon 22 of 25	ENSP00000475522.1	U3KQ39

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457896

Hom.:

Cov.:

AF XY:

0.00000138

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:

0.0000252

AC:

AN:

39628

South Asian (SAS)

AF:

0.00

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:

0.00

AC:

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0082

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.28

M_CAP

Benign

0.0035

MetaRNN

Benign

0.031

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

0.46

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.1

REVEL

Benign

0.095

Sift

Benign

0.13

Sift4G

Benign

0.13

Polyphen

0.010

Vest4

0.061

MutPred

0.14

Loss of phosphorylation at T943 (P = 0.0016)

MVP

0.099

MPC

0.057

ClinPred

0.15

GERP RS

-0.073

Varity_R

0.050

gMVP

0.14

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over