chr1-177930564-T-C

Variant names:

• chr1-177930564-T-C
• rs77277070
• NM_033127.4:c.3092A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033127.4(SEC16B):​c.3092A>G​(p.Asn1031Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00291 in 1,613,420 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (61 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (45 hom.)
• Consequence: SEC16B NM_033127.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.83
• Publications: 7 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0043646097).
• BP6: Variant 1-177930564-T-C is Benign according to our data. Variant chr1-177930564-T-C is described in ClinVar as Benign. ClinVar VariationId is 786475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC16B	NM_033127.4	MANE Select	c.3092A>G	p.Asn1031Ser	missense	Exon 25 of 26	NP_149118.2	Q96JE7-1
	SEC16B	NM_001390834.1		c.3098A>G	p.Asn1033Ser	missense	Exon 25 of 26	NP_001377763.1
	SEC16B	NM_001390835.1		c.3098A>G	p.Asn1033Ser	missense	Exon 25 of 26	NP_001377764.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC16B	ENST00000308284.11	TSL:1 MANE Select	c.3092A>G	p.Asn1031Ser	missense	Exon 25 of 26	ENSP00000308339.6	Q96JE7-1
	SEC16B	ENST00000528461.5	TSL:1	n.*2079A>G		non_coding_transcript_exon	Exon 24 of 25	ENSP00000475522.1	U3KQ39
	SEC16B	ENST00000528461.5	TSL:1	n.*2079A>G		3_prime_UTR	Exon 24 of 25	ENSP00000475522.1	U3KQ39

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2361 AN: 151960 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00375 AC: 934 AN: 248846 AF XY: 0.00287

Gnomad AFR exome AF: 0.0530

Gnomad AMR exome AF: 0.00223

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.00159 AC: 2324 AN: 1461342 Hom.: 45 Cov.: 30 AF XY: 0.00135 AC XY: 984 AN XY: 726952

African (AFR) AF: 0.0531 AC: 1776 AN: 33452

American (AMR) AF: 0.00242 AC: 108 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.000650 AC: 17 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39694

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00364 AC: 21 AN: 5764

European-Non Finnish (NFE) AF: 0.000133 AC: 148 AN: 1111708

Other (OTH) AF: 0.00384 AC: 232 AN: 60362

GnomAD4 genome AF: 0.0155 AC: 2364 AN: 152078 Hom.: 61 Cov.: 32 AF XY: 0.0148 AC XY: 1102 AN XY: 74350

African (AFR) AF: 0.0543 AC: 2252 AN: 41470

American (AMR) AF: 0.00497 AC: 76 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67990

Other (OTH) AF: 0.0104 AC: 22 AN: 2108

Alfa AF: 0.00653 Hom.: 52

Bravo AF: 0.0174

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0456 AC: 172

ESP6500EA AF: 0.000243 AC: 2

ExAC AF: 0.00440 AC: 532

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.8
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.064	T
Polyphen		1.0	D
Vest4		0.36
MVP		0.68
MPC		0.26
ClinPred		0.032	T
GERP RS		5.5
Varity_R		0.51
gMVP		0.43
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs77277070; hg19: chr1-177899699; COSMIC: COSV99045489; COSMIC: COSV99045489;