rs150007923

Variant names:

• chr14-77507370-G-A
• rs150007923
• NM_004863.4:c.*4914C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-77507370-G-A
• chr14-77507370-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004863.4(SPTLC2):​c.*4914C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 147,488 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (140 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPTLC2 NM_004863.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.53
• Publications: 1 publications found

Genes affected

SPTLC2 (HGNC:11278): (serine palmitoyltransferase long chain base subunit 2) This gene encodes a long chain base subunit of serine palmitoyltransferase. Serine palmitoyltransferase, which consists of two different subunits, is the key enzyme in sphingolipid biosynthesis. It catalyzes the pyridoxal-5-prime-phosphate-dependent condensation of L-serine and palmitoyl-CoA to 3-oxosphinganine. Mutations in this gene were identified in patients with hereditary sensory neuropathy type I. [provided by RefSeq, Mar 2011]

SPTLC2 Gene-Disease associations (from GenCC):

• neuropathy, hereditary sensory and autonomic, type 1C

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, G2P, ClinGen
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: STRONG Submitted by: ClinGen
• hereditary sensory and autonomic neuropathy type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 14-77507370-G-A is Benign according to our data. Variant chr14-77507370-G-A is described in ClinVar as Benign. ClinVar VariationId is 314581.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004863.4. 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
	SPTLC2	NM_004863.4	MANE Select	c.*4914C>T		3_prime_UTR	Exon 12 of 12	NP_004854.1	O15270

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTLC2	ENST00000216484.7	TSL:1 MANE Select	c.*4914C>T		3_prime_UTR	Exon 12 of 12	ENSP00000216484.2	O15270
	SPTLC2	ENST00000686627.1		n.5635C>T		non_coding_transcript_exon	Exon 5 of 5
	SPTLC2	ENST00000687688.1		n.6366C>T		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes AF: 0.0253 AC: 3735 AN: 147396 Hom.: 140 Cov.: 31

Gnomad AFR AF: 0.0904

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00730

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000198

Gnomad SAS AF: 0.000640

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000341

Gnomad OTH AF: 0.0187

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 86 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 60

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

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) AF: 0.00 AC: 0 AN: 72

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0254 AC: 3739 AN: 147488 Hom.: 140 Cov.: 31 AF XY: 0.0243 AC XY: 1737 AN XY: 71576

African (AFR) AF: 0.0903 AC: 3569 AN: 39522

American (AMR) AF: 0.00722 AC: 105 AN: 14538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.000198 AC: 1 AN: 5048

South Asian (SAS) AF: 0.000642 AC: 3 AN: 4676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000341 AC: 23 AN: 67412

Other (OTH) AF: 0.0185 AC: 38 AN: 2054

Alfa AF: 0.0226 Hom.: 11

Bravo AF: 0.0283

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.86
DANN	Benign	0.16
PhyloP100		-1.5
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: rs150007923; hg19: chr14-77973713;