1-231241297-G-A

Variant names:

• chr1-231241297-G-A
• rs748285545
• NM_014236.4:c.-82G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014236.4(GNPAT):​c.-82G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000315 in 1,270,868 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: GNPAT NM_014236.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.784
• 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]

FSAF1 (HGNC:25332): (chromosome 1 open reading frame 131) Enables RNA binding activity. Located in chromosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014236.4. 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
	GNPAT	NM_014236.4	MANE Select	c.-82G>A		5_prime_UTR	Exon 1 of 16	NP_055051.1	O15228-1
	GNPAT	NM_001316350.2		c.-82G>A		5_prime_UTR	Exon 1 of 15	NP_001303279.1	O15228-2
	FSAF1	NM_152379.4	MANE Select	c.-156C>T		upstream_gene	N/A	NP_689592.2	Q8NDD1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPAT	ENST00000366647.9	TSL:1 MANE Select	c.-82G>A		5_prime_UTR	Exon 1 of 16	ENSP00000355607.4	O15228-1
	GNPAT	ENST00000851685.1		c.-82G>A		5_prime_UTR	Exon 1 of 16	ENSP00000521744.1
	GNPAT	ENST00000926541.1		c.-82G>A		5_prime_UTR	Exon 1 of 16	ENSP00000596600.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000315 AC: 4 AN: 1270868 Hom.: 0 Cov.: 19 AF XY: 0.00000312 AC XY: 2 AN XY: 641998

African (AFR) AF: 0.00 AC: 0 AN: 29618

American (AMR) AF: 0.00 AC: 0 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24882

East Asian (EAS) AF: 0.00 AC: 0 AN: 38806

South Asian (SAS) AF: 0.00 AC: 0 AN: 82462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5444

European-Non Finnish (NFE) AF: 0.00000427 AC: 4 AN: 937818

Other (OTH) AF: 0.00 AC: 0 AN: 54132

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		0.78
PromoterAI		-0.064	Neutral

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: rs748285545; hg19: chr1-231377043;