dbSNP rs777861102: SEC16B:p.Arg892Pro (chr1-177933533-C-G) – 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.2675G>C(p.Arg892Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,570 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. R892Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SEC16B
NM_033127.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04926449).

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.2675G>C	p.Arg892Pro	missense	Exon 21 of 26	NP_149118.2	Q96JE7-1
SEC16B	NM_001390834.1		c.2678G>C	p.Arg893Pro	missense	Exon 21 of 26	NP_001377763.1
SEC16B	NM_001390835.1		c.2678G>C	p.Arg893Pro	missense	Exon 21 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.2675G>C	p.Arg892Pro	missense	Exon 21 of 26	ENSP00000308339.6	Q96JE7-1
SEC16B	ENST00000528461.5	TSL:1	n.*1662G>C		non_coding_transcript_exon	Exon 20 of 25	ENSP00000475522.1	U3KQ39
SEC16B	ENST00000528461.5	TSL:1	n.*1662G>C		3_prime_UTR	Exon 20 of 25	ENSP00000475522.1	U3KQ39

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461570

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727056

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111816

Other (OTH)

AF:

0.00

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.067

(source)

DANN

Benign

0.49

DEOGEN2

Benign

0.0026

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.32

M_CAP

Benign

0.0014

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

PhyloP100

-1.5

PrimateAI

Benign

0.17

PROVEAN

Benign

1.5

REVEL

Benign

0.028

Sift

Benign

0.50

Sift4G

Benign

0.32

Polyphen

0.0

Vest4

0.067

MutPred

0.39

Loss of MoRF binding (P = 0.0028)

MVP

0.040

MPC

0.049

ClinPred

0.058

GERP RS

-11

Varity_R

0.089

gMVP

0.13

Mutation Taster

=95/5

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over