chr17-46929562-G-T

Variant names:

• chr17-46929562-G-T
• rs145772886
• NM_004287.5:c.72G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004287.5(GOSR2):​c.72G>T​(p.Thr24Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,397,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T24T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GOSR2 NM_004287.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• 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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05812207).
• BP7: Synonymous conserved (PhyloP=-0.691 with no splicing effect.

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.72G>T	p.Thr24Thr	synonymous	Exon 2 of 6	NP_004278.2
	GOSR2	NM_001321133.2		c.72G>T	p.Thr24Thr	synonymous	Exon 2 of 7	NP_001308062.1	I3NI02
	GOSR2	NM_054022.4		c.72G>T	p.Thr24Thr	synonymous	Exon 2 of 7	NP_473363.1	O14653-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOSR2	ENST00000640051.2	TSL:1 MANE Select	c.72G>T	p.Thr24Thr	synonymous	Exon 2 of 6	ENSP00000492751.1	O14653-1
	GOSR2	ENST00000225567.9	TSL:1	c.72G>T	p.Thr24Thr	synonymous	Exon 2 of 7	ENSP00000225567.4	O14653-2
	GOSR2	ENST00000640621.1	TSL:1	c.72G>T	p.Thr24Thr	synonymous	Exon 2 of 5	ENSP00000492830.1	O14653-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1397420 Hom.: 0 Cov.: 24 AF XY: 0.00000143 AC XY: 1 AN XY: 698970

African (AFR) AF: 0.00 AC: 0 AN: 32172

American (AMR) AF: 0.00 AC: 0 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25752

East Asian (EAS) AF: 0.00 AC: 0 AN: 39404

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 84982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5642

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1053242

Other (OTH) AF: 0.00 AC: 0 AN: 58306

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.19
DANN	Benign	0.79
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.058	T
PhyloP100		-0.69
GERP RS		-6.0
PromoterAI		0.0090	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6

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: rs145772886; hg19: chr17-45006928;