rs141265918

Variant names:

• chr9-92080056-G-A
• rs141265918
• NM_006415.4:c.387C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-92080056-G-A
• chr9-92080056-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_006415.4(SPTLC1):​c.387C>T​(p.Gly129Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000618 in 1,613,916 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00064 (7 hom.)
• Consequence: SPTLC1 NM_006415.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.42
• Publications: 0 publications found

Genes affected

SPTLC1 (HGNC:11277): (serine palmitoyltransferase long chain base subunit 1) This gene encodes a member of the class-II pyridoxal-phosphate-dependent aminotransferase family. The encoded protein is the long chain base subunit 1 of serine palmitoyltransferase. Serine palmitoyltransferase converts L-serine and palmitoyl-CoA to 3-oxosphinganine with pyridoxal 5'-phosphate and is the key enzyme in sphingolipid biosynthesis. Mutations in this gene were identified in patients with hereditary sensory neuropathy type 1. Alternatively spliced variants encoding different isoforms have been identified. Pseudogenes of this gene have been defined on chromosomes 1, 6, 10, and 13. [provided by RefSeq, Jul 2013]

SPTLC1 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis 27, juvenile

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• neuropathy, hereditary sensory and autonomic, type 1A

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• hereditary sensory and autonomic neuropathy type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 9-92080056-G-A is Benign according to our data. Variant chr9-92080056-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 367551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000394 (60/152200) while in subpopulation SAS AF = 0.0087 (42/4828). AF 95% confidence interval is 0.00661. There are 0 homozygotes in GnomAd4. There are 45 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 60 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006415.4. 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
	SPTLC1	NM_006415.4	MANE Select	c.387C>T	p.Gly129Gly	synonymous	Exon 5 of 15	NP_006406.1	O15269-1
	SPTLC1	NM_001281303.2		c.387C>T	p.Gly129Gly	synonymous	Exon 5 of 15	NP_001268232.1
	SPTLC1	NM_178324.3		c.387C>T	p.Gly129Gly	synonymous	Exon 5 of 6	NP_847894.1	O15269-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTLC1	ENST00000262554.7	TSL:1 MANE Select	c.387C>T	p.Gly129Gly	synonymous	Exon 5 of 15	ENSP00000262554.2	O15269-1
	SPTLC1	ENST00000337841.4	TSL:1	c.387C>T	p.Gly129Gly	synonymous	Exon 5 of 6	ENSP00000337635.4	O15269-2
	SPTLC1	ENST00000953500.1		c.597C>T	p.Gly199Gly	synonymous	Exon 6 of 16	ENSP00000623559.1

Frequencies

GnomAD3 genomes AF: 0.000401 AC: 61 AN: 152080 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00890

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00127 AC: 319 AN: 251328 AF XY: 0.00175

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.000642 AC: 938 AN: 1461716 Hom.: 7 Cov.: 30 AF XY: 0.000924 AC XY: 672 AN XY: 727176

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

American (AMR) AF: 0.000224 AC: 10 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00799 AC: 689 AN: 86248

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53376

Middle Eastern (MID) AF: 0.00711 AC: 41 AN: 5764

European-Non Finnish (NFE) AF: 0.000134 AC: 149 AN: 1111910

Other (OTH) AF: 0.000762 AC: 46 AN: 60392

GnomAD4 genome AF: 0.000394 AC: 60 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.000605 AC XY: 45 AN XY: 74402

African (AFR) AF: 0.0000241 AC: 1 AN: 41530

American (AMR) AF: 0.000131 AC: 2 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00870 AC: 42 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68010

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.000164 Hom.: 0

Bravo AF: 0.000174

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Charcot-Marie-Tooth disease (1)
-	-	1	Hereditary sensory and autonomic neuropathy type 1 (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	Neuropathy, hereditary sensory and autonomic, type 1A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.21
DANN	Benign	0.56
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.30		Position offset: 32

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs141265918; hg19: chr9-94842338; COSMIC: COSV52763531;