NM_001144757.3:c.376+138G>A

Variant names:

• chr15-32680053-G-A
• rs75242289
• NM_001144757.3:c.376+138G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001144757.3(SCG5):​c.376+138G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 774,472 control chromosomes in the GnomAD database, including 1,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (236 hom., cov: 32)
  • Exomes 𝑓: 0.055 (1231 hom.)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0190
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-32680053-G-A is Benign according to our data. Variant chr15-32680053-G-A is described in ClinVar as Benign. ClinVar VariationId is 1236383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0681 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.376+138G>A		intron	N/A	NP_001138229.1	P05408-1
	ARHGAP11A-SCG5	NM_001368319.1		c.1618+138G>A		intron	N/A	NP_001355248.1	A0A8I5KWH8
	SCG5	NM_003020.5		c.376+138G>A		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.376+138G>A		intron	N/A	ENSP00000300175.4	P05408-1
	ARHGAP11A-SCG5	ENST00000692248.1		c.1618+138G>A		intron	N/A	ENSP00000510771.1	A0A8I5KWH8
	SCG5	ENST00000413748.6	TSL:1	c.376+138G>A		intron	N/A	ENSP00000388560.2	P05408-2

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 7159 AN: 152122 Hom.: 236 Cov.: 32

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0499

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00850

Gnomad FIN AF: 0.0581

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0698

Gnomad OTH AF: 0.0479

GnomAD4 exome AF: 0.0550 AC: 34193 AN: 622232 Hom.: 1231 AF XY: 0.0535 AC XY: 17269 AN XY: 322578

African (AFR) AF: 0.0173 AC: 275 AN: 15918

American (AMR) AF: 0.0390 AC: 874 AN: 22394

Ashkenazi Jewish (ASJ) AF: 0.0374 AC: 540 AN: 14428

East Asian (EAS) AF: 0.0000882 AC: 3 AN: 34018

South Asian (SAS) AF: 0.00718 AC: 325 AN: 45240

European-Finnish (FIN) AF: 0.0523 AC: 1880 AN: 35970

Middle Eastern (MID) AF: 0.0245 AC: 55 AN: 2248

European-Non Finnish (NFE) AF: 0.0680 AC: 28595 AN: 420476

Other (OTH) AF: 0.0522 AC: 1646 AN: 31540

GnomAD4 genome AF: 0.0470 AC: 7159 AN: 152240 Hom.: 236 Cov.: 32 AF XY: 0.0453 AC XY: 3371 AN XY: 74452

African (AFR) AF: 0.0179 AC: 743 AN: 41536

American (AMR) AF: 0.0498 AC: 762 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 129 AN: 3470

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

South Asian (SAS) AF: 0.00871 AC: 42 AN: 4820

European-Finnish (FIN) AF: 0.0581 AC: 617 AN: 10612

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0698 AC: 4747 AN: 68012

Other (OTH) AF: 0.0474 AC: 100 AN: 2110

Alfa AF: 0.0556 Hom.: 39

Bravo AF: 0.0457

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.62
PhyloP100		-0.019
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: rs75242289; hg19: chr15-32972254;