rs11790991

Variant names:

• chr9-92111042-A-G
• rs11790991
• NM_006415.4:c.165+1413T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006415.4(SPTLC1):​c.165+1413T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,132 control chromosomes in the GnomAD database, including 2,302 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2302 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPTLC1 NM_006415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 2 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]

MTND4P15 (HGNC:42202): (MT-ND4 pseudogene 15)

MTND4LP7 (HGNC:42241): (MT-ND4L pseudogene 7)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTLC1	NM_006415.4	c.165+1413T>C		intron_variant	Intron 2 of 14	ENST00000262554.7	NP_006406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTLC1	ENST00000262554.7	c.165+1413T>C		intron_variant	Intron 2 of 14	1	NM_006415.4	ENSP00000262554.2

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24588 AN: 152014 Hom.: 2297 Cov.: 32

Gnomad AFR AF: 0.0695

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0656

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.163

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

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: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.162 AC: 24594 AN: 152132 Hom.: 2302 Cov.: 32 AF XY: 0.162 AC XY: 12021 AN XY: 74364

African (AFR) AF: 0.0693 AC: 2877 AN: 41518

American (AMR) AF: 0.212 AC: 3237 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3470

East Asian (EAS) AF: 0.0653 AC: 339 AN: 5190

South Asian (SAS) AF: 0.184 AC: 886 AN: 4824

European-Finnish (FIN) AF: 0.178 AC: 1878 AN: 10572

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14056 AN: 67974

Other (OTH) AF: 0.160 AC: 336 AN: 2102

Alfa AF: 0.178 Hom.: 1027

Bravo AF: 0.160

Asia WGS AF: 0.120 AC: 418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.7
DANN	Benign	0.89
PhyloP100		-1.2
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: rs11790991; hg19: chr9-94873324;