NM_001144757.3:c.-7-60T>C

Variant names:

• chr15-32643526-T-C
• rs79291170
• NM_001144757.3:c.-7-60T>C

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.-7-60T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,325,932 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (87 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (69 hom.)
• Consequence: SCG5 NM_001144757.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0730
• Publications: 0 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=-0.81).
• BP6: Variant 15-32643526-T-C is Benign according to our data. Variant chr15-32643526-T-C is described in ClinVar as Benign. ClinVar VariationId is 1270848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0607 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.-7-60T>C		intron	N/A	NP_001138229.1	P05408-1
	ARHGAP11A-SCG5	NM_001368319.1		c.1236-60T>C		intron	N/A	NP_001355248.1	A0A8I5KWH8
	SCG5	NM_003020.5		c.-7-60T>C		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.-7-60T>C		intron	N/A	ENSP00000300175.4	P05408-1
	ARHGAP11A-SCG5	ENST00000692248.1		c.1236-60T>C		intron	N/A	ENSP00000510771.1	A0A8I5KWH8
	SCG5	ENST00000413748.6	TSL:1	c.-7-60T>C		intron	N/A	ENSP00000388560.2	P05408-2

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2709 AN: 152160 Hom.: 88 Cov.: 32

Gnomad AFR AF: 0.0627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.00192 AC: 2251 AN: 1173654 Hom.: 69 AF XY: 0.00158 AC XY: 933 AN XY: 592048

African (AFR) AF: 0.0642 AC: 1792 AN: 27918

American (AMR) AF: 0.00380 AC: 167 AN: 43918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24114

East Asian (EAS) AF: 0.00 AC: 0 AN: 37902

South Asian (SAS) AF: 0.000212 AC: 17 AN: 80196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52378

Middle Eastern (MID) AF: 0.00236 AC: 12 AN: 5076

European-Non Finnish (NFE) AF: 0.0000693 AC: 59 AN: 851528

Other (OTH) AF: 0.00403 AC: 204 AN: 50624

GnomAD4 genome AF: 0.0178 AC: 2714 AN: 152278 Hom.: 87 Cov.: 32 AF XY: 0.0175 AC XY: 1302 AN XY: 74474

African (AFR) AF: 0.0627 AC: 2604 AN: 41550

American (AMR) AF: 0.00503 AC: 77 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68022

Other (OTH) AF: 0.0118 AC: 25 AN: 2112

Alfa AF: 0.0155 Hom.: 5

Bravo AF: 0.0205

Asia WGS AF: 0.00173 AC: 6 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	-0.81
CADD	Benign	3.0
DANN	Benign	0.65
PhyloP100		0.073
PromoterAI		0.0074	Neutral
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: rs79291170; hg19: chr15-32935727;