NM_001144757.3:c.489+231A>G

Variant names:

• chr15-32684900-A-G
• rs7165737
• NM_001144757.3:c.489+231A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001144757.3(SCG5):​c.489+231A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,070 control chromosomes in the GnomAD database, including 28,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.61 (28286 hom., cov: 32)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.67
• Publications: 6 publications found

Genes affected

SCG5 (HGNC:10816): (secretogranin V) This gene encodes a secreted chaperone protein that prevents the aggregation of other secreted proteins, including proteins that are associated with neurodegenerative and metabolic disease. The encoded protein may be best known for its role in the trafficking and activation of prohormone convertase PC2 (encoded by Gene ID: 5126). Phosphorylation of the encoded protein has been shown to have an inhibitory effect on its chaperone function. This gene also produces a ARHGAP11A-SCG5 readthrough transcript and ARHGAP11A-SCG5 protein. [provided by RefSeq, Feb 2019]

ARHGAP11A-SCG5 (HGNC:56310): (ARHGAP11A-SCG5 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring ARHGAP11A (Rho GTPase activating protein 11A) and SCG5 (secretogranin V) genes on chromosome 15q13.3. The readthrough transcript encodes a fusion protein that shares sequence identity with both the ARHGAP11A and SCG5 gene products. [provided by RefSeq, Feb 2019]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-32684900-A-G is Benign according to our data. Variant chr15-32684900-A-G is described in ClinVar as Benign. ClinVar VariationId is 1235123.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144757.3. 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
	SCG5	NM_001144757.3	MANE Select	c.489+231A>G		intron	N/A	NP_001138229.1	P05408-1
	ARHGAP11A-SCG5	NM_001368319.1		c.1728+231A>G		intron	N/A	NP_001355248.1	A0A8I5KWH8
	SCG5	NM_003020.5		c.486+231A>G		intron	N/A	NP_003011.1	P05408-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCG5	ENST00000300175.9	TSL:1 MANE Select	c.489+231A>G		intron	N/A	ENSP00000300175.4	P05408-1
	ARHGAP11A-SCG5	ENST00000692248.1		c.1728+231A>G		intron	N/A	ENSP00000510771.1	A0A8I5KWH8
	SCG5	ENST00000413748.6	TSL:1	c.486+231A>G		intron	N/A	ENSP00000388560.2	P05408-2

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92349 AN: 151950 Hom.: 28264 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.622

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.608 AC: 92407 AN: 152070 Hom.: 28286 Cov.: 32 AF XY: 0.609 AC XY: 45286 AN XY: 74334

African (AFR) AF: 0.537 AC: 22278 AN: 41452

American (AMR) AF: 0.586 AC: 8950 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2195 AN: 3472

East Asian (EAS) AF: 0.669 AC: 3466 AN: 5180

South Asian (SAS) AF: 0.608 AC: 2933 AN: 4822

European-Finnish (FIN) AF: 0.659 AC: 6967 AN: 10578

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43613 AN: 67970

Other (OTH) AF: 0.620 AC: 1309 AN: 2112

Alfa AF: 0.627 Hom.: 27327

Bravo AF: 0.597

Asia WGS AF: 0.637 AC: 2213 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0050
DANN	Benign	0.42
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs7165737; hg19: chr15-32977101;