Genetic Variant NM_033127.4:c.2978C>T (chr1-177932524-G-A) – 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.2978C>T(p.Ala993Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000494 in 1,557,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

SEC16B
NM_033127.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.552

Publications

1 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=0.045935452).

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.2978C>T	p.Ala993Val	missense	Exon 24 of 26	NP_149118.2	Q96JE7-1
SEC16B	NM_001390834.1		c.2984C>T	p.Ala995Val	missense	Exon 24 of 26	NP_001377763.1
SEC16B	NM_001390835.1		c.2984C>T	p.Ala995Val	missense	Exon 24 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.2978C>T	p.Ala993Val	missense	Exon 24 of 26	ENSP00000308339.6	Q96JE7-1
SEC16B	ENST00000528461.5	TSL:1	n.*1965C>T		non_coding_transcript_exon	Exon 23 of 25	ENSP00000475522.1	U3KQ39
SEC16B	ENST00000528461.5	TSL:1	n.*1965C>T		3_prime_UTR	Exon 23 of 25	ENSP00000475522.1	U3KQ39

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000544

AC:

AN:

165424

AF XY:

0.0000682

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000864

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000296

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

AF:

0.0000534

AC:

AN:

1405234

Hom.:

Cov.:

AF XY:

0.0000620

AC XY:

AN XY:

694048

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31538

American (AMR)

AF:

0.00

AC:

AN:

36994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24868

East Asian (EAS)

AF:

0.0000557

AC:

AN:

35932

South Asian (SAS)

AF:

0.000342

AC:

AN:

78948

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49818

Middle Eastern (MID)

AF:

0.000353

AC:

AN:

5672

European-Non Finnish (NFE)

AF:

0.0000369

AC:

AN:

1083224

Other (OTH)

AF:

0.0000687

AC:

AN:

58240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

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:

0.0000131

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000525

AC:

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

0.090

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

9.0

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0039

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.40

M_CAP

Benign

0.0029

MetaRNN

Benign

0.046

MetaSVM

Benign

-0.97

PhyloP100

0.55

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.4

REVEL

Benign

0.023

Sift

Uncertain

0.027

Sift4G

Benign

0.62

Polyphen

0.043

Vest4

0.20

MutPred

0.13

Gain of MoRF binding (P = 0.2497)

MVP

0.048

MPC

0.042

ClinPred

0.32

GERP RS

-1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.039

gMVP

0.12

Mutation Taster

=96/4

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