chr9-92031163-A-C

Variant names:

• chr9-92031163-A-C
• rs7035964
• NM_006415.4:c.*1302T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_006415.4(SPTLC1):​c.*1302T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,638 control chromosomes in the GnomAD database, including 1,879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1879 hom., cov: 32)
  • Exomes 𝑓: 0.012 (0 hom.)
• Consequence: SPTLC1 NM_006415.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.75
• Publications: 4 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• neuropathy, hereditary sensory and autonomic, type 1A

  Inheritance: AD Classification: STRONG Submitted by: 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 9-92031163-A-C is Benign according to our data. Variant chr9-92031163-A-C is described in ClinVar as Benign. ClinVar VariationId is 367526.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

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.*1302T>G		3_prime_UTR	Exon 15 of 15	NP_006406.1	O15269-1
	SPTLC1	NM_001281303.2		c.*1150T>G		3_prime_UTR	Exon 15 of 15	NP_001268232.1
	SPTLC1	NM_001368272.1		c.*1302T>G		3_prime_UTR	Exon 16 of 16	NP_001355201.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTLC1	ENST00000262554.7	TSL:1 MANE Select	c.*1302T>G		3_prime_UTR	Exon 15 of 15	ENSP00000262554.2	O15269-1
	SPTLC1	ENST00000953500.1		c.*1302T>G		3_prime_UTR	Exon 16 of 16	ENSP00000623559.1
	SPTLC1	ENST00000687972.1		c.*1302T>G		3_prime_UTR	Exon 16 of 16	ENSP00000509208.1	A0A8I5QKQ8

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16285 AN: 152092 Hom.: 1874 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0551

Gnomad ASJ AF: 0.0531

Gnomad EAS AF: 0.0323

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.0251

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.0816

GnomAD4 exome AF: 0.0117 AC: 5 AN: 428 Hom.: 0 Cov.: 0 AF XY: 0.00781 AC XY: 2 AN XY: 256

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0118 AC: 5 AN: 422

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.107 AC: 16311 AN: 152210 Hom.: 1879 Cov.: 32 AF XY: 0.104 AC XY: 7747 AN XY: 74412

African (AFR) AF: 0.295 AC: 12252 AN: 41482

American (AMR) AF: 0.0549 AC: 841 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0531 AC: 184 AN: 3468

East Asian (EAS) AF: 0.0323 AC: 168 AN: 5194

South Asian (SAS) AF: 0.0611 AC: 295 AN: 4828

European-Finnish (FIN) AF: 0.0251 AC: 266 AN: 10614

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0309 AC: 2101 AN: 68006

Other (OTH) AF: 0.0807 AC: 170 AN: 2106

Alfa AF: 0.0605 Hom.: 173

Bravo AF: 0.117

Asia WGS AF: 0.0710 AC: 246 AN: 3460

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Neuropathy, hereditary sensory and autonomic, type 1A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Benign	0.87
PhyloP100		1.8

Splicing

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

Other links and lift over

dbSNP: rs7035964; hg19: chr9-94793445; COSMIC: COSV52768218;