Genetic Variant SEC16B:p.Ala986Pro (chr1-177932546-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.2956G>C(p.Ala986Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000639 in 1,409,084 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. 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. A986T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

SEC16B
NM_033127.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.927

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=0.06056261).

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.2956G>C	p.Ala986Pro	missense	Exon 24 of 26	NP_149118.2	Q96JE7-1
SEC16B	NM_001390834.1		c.2962G>C	p.Ala988Pro	missense	Exon 24 of 26	NP_001377763.1
SEC16B	NM_001390835.1		c.2962G>C	p.Ala988Pro	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.2956G>C	p.Ala986Pro	missense	Exon 24 of 26	ENSP00000308339.6	Q96JE7-1
SEC16B	ENST00000528461.5	TSL:1	n.*1943G>C		non_coding_transcript_exon	Exon 23 of 25	ENSP00000475522.1	U3KQ39
SEC16B	ENST00000528461.5	TSL:1	n.*1943G>C		3_prime_UTR	Exon 23 of 25	ENSP00000475522.1	U3KQ39

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000588

AC:

AN:

169952

AF XY:

0.0000111

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:

0.000218

GnomAD4 exome

AF:

0.00000639

AC:

AN:

1409084

Hom.:

Cov.:

AF XY:

0.00000575

AC XY:

AN XY:

696166

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31634

American (AMR)

AF:

0.00

AC:

AN:

37726

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24954

East Asian (EAS)

AF:

0.00

AC:

AN:

36052

South Asian (SAS)

AF:

0.0000253

AC:

AN:

79166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50056

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00000461

AC:

AN:

1085430

Other (OTH)

AF:

0.0000171

AC:

AN:

58382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

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.:

Alfa

AF:

0.0000194

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.44

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.0052

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.33

M_CAP

Benign

0.0029

MetaRNN

Benign

0.061

MetaSVM

Benign

-1.0

PhyloP100

-0.93

PrimateAI

Benign

0.33

PROVEAN

Benign

0.28

REVEL

Benign

0.037

Sift

Benign

0.17

Sift4G

Benign

0.29

Polyphen

0.41

Vest4

0.21

MutPred

0.29

Gain of glycosylation at A986 (P = 0.0423)

MVP

0.040

MPC

0.046

ClinPred

0.13

GERP RS

-6.2

Varity_R

0.070

gMVP

0.14

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

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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