rs193920851

Variant names:

• chr1-231275496-G-A
• rs193920851
• NM_014236.4:c.1935G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-231275496-G-A
• chr1-231275496-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014236.4(GNPAT):​c.1935G>A​(p.Lys645Lys) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,414,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GNPAT NM_014236.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.00003929
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• Publications: 0 publications found

Genes affected

GNPAT (HGNC:4416): (glyceronephosphate O-acyltransferase) This gene encodes an enzyme located in the peroxisomal membrane which is essential to the synthesis of ether phospholipids. Mutations in this gene are associated with rhizomelic chondrodysplasia punctata. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

GNPAT Gene-Disease associations (from GenCC):

• glyceronephosphate O-acyltransferase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• rhizomelic chondrodysplasia punctata type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=1.2 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNPAT	NM_014236.4	c.1935G>A	p.Lys645Lys	splice_region_variant, synonymous_variant	Exon 14 of 16	ENST00000366647.9	NP_055051.1
GNPAT	NM_001316350.2	c.1752G>A	p.Lys584Lys	splice_region_variant, synonymous_variant	Exon 13 of 15		NP_001303279.1
GNPAT	XM_005273313.5	c.1932G>A	p.Lys644Lys	splice_region_variant, synonymous_variant	Exon 14 of 16		XP_005273370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNPAT	ENST00000366647.9	c.1935G>A	p.Lys645Lys	splice_region_variant, synonymous_variant	Exon 14 of 16	1	NM_014236.4	ENSP00000355607.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1414796 Hom.: 0 Cov.: 24 AF XY: 0.00000142 AC XY: 1 AN XY: 706592

African (AFR) AF: 0.00 AC: 0 AN: 32644

American (AMR) AF: 0.00 AC: 0 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25838

East Asian (EAS) AF: 0.00 AC: 0 AN: 39490

South Asian (SAS) AF: 0.00 AC: 0 AN: 85254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1068980

Other (OTH) AF: 0.00 AC: 0 AN: 58850

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.6
DANN	Benign	0.76
PhyloP100		1.2
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000039
dbscSNV1_RF	Benign	0.010
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: rs193920851; hg19: chr1-231411242;