NM_004287.5:c.29+8C>T

Variant names:

• chr17-46923229-C-T
• rs573306680
• NM_004287.5:c.29+8C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP6

The NM_004287.5(GOSR2):​c.29+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000215 in 1,550,752 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: GOSR2 NM_004287.5 splice_region, intron
• Scores: Splicing: ADA: 0.00009518
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3 B:2
• Conservation: PhyloP100: 0.215
• Publications: 0 publications found

Genes affected

GOSR2 (HGNC:4431): (golgi SNAP receptor complex member 2) This gene encodes a trafficking membrane protein which transports proteins among the medial- and trans-Golgi compartments. Due to its chromosomal location and trafficking function, this gene may be involved in familial essential hypertension. [provided by RefSeq, Mar 2016]

ENSG00000262633 (HGNC:):

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

GOSR2-DT (HGNC:55346): (GOSR2 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 17-46923229-C-T is Benign according to our data. Variant chr17-46923229-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 137489.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004287.5. 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
	GOSR2	NM_004287.5	MANE Select	c.29+8C>T		splice_region intron	N/A	NP_004278.2
	GOSR2	NM_001363851.2		c.-429C>T		5_prime_UTR	Exon 1 of 6	NP_001350780.1	A0A1W2PRL0
	GOSR2	NM_001321134.2		c.-66C>T		5_prime_UTR	Exon 1 of 5	NP_001308063.1	A0A1W2PQE0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOSR2	ENST00000640051.2	TSL:1 MANE Select	c.29+8C>T		splice_region intron	N/A	ENSP00000492751.1	O14653-1
	GOSR2	ENST00000225567.9	TSL:1	c.29+8C>T		splice_region intron	N/A	ENSP00000225567.4	O14653-2
	GOSR2	ENST00000640621.1	TSL:1	c.29+8C>T		splice_region intron	N/A	ENSP00000492830.1	O14653-3

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000235 AC: 36 AN: 153094 AF XY: 0.000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000712

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000262

Gnomad NFE exome AF: 0.000448

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000207 AC: 289 AN: 1398406 Hom.: 1 Cov.: 31 AF XY: 0.000223 AC XY: 154 AN XY: 689826

African (AFR) AF: 0.00 AC: 0 AN: 31580

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.000835 AC: 21 AN: 25164

East Asian (EAS) AF: 0.00 AC: 0 AN: 35730

South Asian (SAS) AF: 0.00 AC: 0 AN: 79222

European-Finnish (FIN) AF: 0.000265 AC: 13 AN: 49124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.000232 AC: 250 AN: 1078234

Other (OTH) AF: 0.0000863 AC: 5 AN: 57962

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152346 Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15 AN XY: 74500

African (AFR) AF: 0.00 AC: 0 AN: 41592

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68038

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000367 Hom.: 0

Bravo AF: 0.000253

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)
-	-	1	not specified (1)
-	-	1	Progressive myoclonic epilepsy (1)
-	1	-	Progressive myoclonic epilepsy type 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Benign	0.92
PhyloP100		0.21
PromoterAI		0.023	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000095
dbscSNV1_RF	Benign	0.012
SpliceAI score (max)		0.48		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.48		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs573306680; hg19: chr17-45000595;