NM_001144757.3:c.-32A>T

Variant names:

• chr15-32641754-A-T
• rs13850
• NM_001144757.3:c.-32A>T

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.-32A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,322 control chromosomes in the GnomAD database, including 1,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1119 hom., cov: 32)
  • Exomes 𝑓: 0.21 (3 hom.)
• Consequence: SCG5 NM_001144757.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.55
• Publications: 7 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]

ENSG00000285948 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-32641754-A-T is Benign according to our data. Variant chr15-32641754-A-T is described in ClinVar as Benign. ClinVar VariationId is 1287486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCG5	NM_001144757.3	c.-32A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	ENST00000300175.9	NP_001138229.1
SCG5	NM_001144757.3	c.-32A>T		5_prime_UTR_variant	Exon 1 of 6	ENST00000300175.9	NP_001138229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCG5	ENST00000300175.9	c.-32A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	1	NM_001144757.3	ENSP00000300175.4
SCG5	ENST00000300175.9	c.-32A>T		5_prime_UTR_variant	Exon 1 of 6	1	NM_001144757.3	ENSP00000300175.4
ARHGAP11A-SCG5	ENST00000692248.1	c.1236-1832A>T		intron_variant	Intron 9 of 13			ENSP00000510771.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16674 AN: 152086 Hom.: 1119 Cov.: 32

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0164

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.117

GnomAD4 exome AF: 0.207 AC: 24 AN: 116 Hom.: 3 Cov.: 0 AF XY: 0.207 AC XY: 17 AN XY: 82

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.216 AC: 22 AN: 102

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.110 AC: 16671 AN: 152206 Hom.: 1119 Cov.: 32 AF XY: 0.107 AC XY: 7992 AN XY: 74416

African (AFR) AF: 0.0481 AC: 2000 AN: 41554

American (AMR) AF: 0.109 AC: 1662 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3468

East Asian (EAS) AF: 0.0164 AC: 85 AN: 5180

South Asian (SAS) AF: 0.107 AC: 516 AN: 4818

European-Finnish (FIN) AF: 0.129 AC: 1366 AN: 10600

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10219 AN: 67978

Other (OTH) AF: 0.115 AC: 244 AN: 2114

Alfa AF: 0.134 Hom.: 207

Bravo AF: 0.104

Asia WGS AF: 0.0570 AC: 202 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0070
DANN	Benign	0.66
PhyloP100		-3.6
PromoterAI		0.030	Neutral
Mutation Taster		=300/0	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: rs13850; hg19: chr15-32933955;