rs1650610423

Variant names:

• chr1-177933521-T-C
• rs1650610423
• NM_033127.4:c.2687A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_033127.4(SEC16B):​c.2687A>G​(p.Gln896Arg) 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 1,461,582 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. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q896E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SEC16B NM_033127.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.389
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056688756).
• BP6: Variant 1-177933521-T-C is Benign according to our data. Variant chr1-177933521-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3159227.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2687A>G	p.Gln896Arg	missense	Exon 21 of 26	NP_149118.2	Q96JE7-1
	SEC16B	NM_001390834.1		c.2690A>G	p.Gln897Arg	missense	Exon 21 of 26	NP_001377763.1
	SEC16B	NM_001390835.1		c.2690A>G	p.Gln897Arg	missense	Exon 21 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.2687A>G	p.Gln896Arg	missense	Exon 21 of 26	ENSP00000308339.6	Q96JE7-1
	SEC16B	ENST00000528461.5	TSL:1	n.*1674A>G		non_coding_transcript_exon	Exon 20 of 25	ENSP00000475522.1	U3KQ39
	SEC16B	ENST00000528461.5	TSL:1	n.*1674A>G		3_prime_UTR	Exon 20 of 25	ENSP00000475522.1	U3KQ39

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461582 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727050

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111824

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.048
DANN	Benign	0.27
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.83	L
PhyloP100		-0.39
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.0050
Sift	Benign	0.18	T
Sift4G	Benign	0.46	T
Polyphen		0.0010	B
Vest4		0.068
MutPred		0.28		Gain of MoRF binding (P = 0.0215)
MVP		0.061
MPC		0.041
ClinPred		0.071	T
GERP RS		-6.2
Varity_R		0.043
gMVP		0.12
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1650610423; hg19: chr1-177902656;