1-177932554-C-G

Variant names:

• chr1-177932554-C-G
• rs907067536
• NM_033127.4:c.2948G>C

Variant summary

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

The NM_033127.4(SEC16B):​c.2948G>C​(p.Arg983Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,407,380 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. R983Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SEC16B NM_033127.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.15
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05600679).

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.2948G>C	p.Arg983Pro	missense	Exon 24 of 26	NP_149118.2	Q96JE7-1
	SEC16B	NM_001390834.1		c.2954G>C	p.Arg985Pro	missense	Exon 24 of 26	NP_001377763.1
	SEC16B	NM_001390835.1		c.2954G>C	p.Arg985Pro	missense	Exon 24 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.2948G>C	p.Arg983Pro	missense	Exon 24 of 26	ENSP00000308339.6	Q96JE7-1
	SEC16B	ENST00000528461.5	TSL:1	n.*1935G>C		non_coding_transcript_exon	Exon 23 of 25	ENSP00000475522.1	U3KQ39
	SEC16B	ENST00000528461.5	TSL:1	n.*1935G>C		3_prime_UTR	Exon 23 of 25	ENSP00000475522.1	U3KQ39

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1407380 Hom.: 0 Cov.: 33 AF XY: 0.00000144 AC XY: 1 AN XY: 695308

African (AFR) AF: 0.00 AC: 0 AN: 31532

American (AMR) AF: 0.00 AC: 0 AN: 37320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24826

East Asian (EAS) AF: 0.00 AC: 0 AN: 36056

South Asian (SAS) AF: 0.00 AC: 0 AN: 78952

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50048

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 9.22e-7 AC: 1 AN: 1084694

Other (OTH) AF: 0.00 AC: 0 AN: 58286

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.0010
DANN	Benign	0.70
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.1	T
PhyloP100		-4.2
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.018
Sift	Benign	0.25	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.33		Loss of methylation at R983 (P = 0.0029)
MVP		0.040
MPC		0.050
ClinPred		0.19	T
GERP RS		-8.9
Varity_R		0.090
gMVP		0.16
Mutation Taster		=92/8	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: rs907067536; hg19: chr1-177901689;