rs113480953

Variant names:

• chr1-231241404-C-G
• rs113480953
• NM_014236.4:c.26C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-231241404-C-G
• chr1-231241404-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014236.4(GNPAT):​c.26C>G​(p.Ser9Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S9F) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GNPAT NM_014236.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09596771).

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.26C>G	p.Ser9Cys	missense	Exon 1 of 16	NP_055051.1
	GNPAT	NM_001316350.2		c.26C>G	p.Ser9Cys	missense	Exon 1 of 15	NP_001303279.1
	FSAF1	NM_152379.4	MANE Select	c.-263G>C		upstream_gene	N/A	NP_689592.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPAT	ENST00000366647.9	TSL:1 MANE Select	c.26C>G	p.Ser9Cys	missense	Exon 1 of 16	ENSP00000355607.4
	GNPAT	ENST00000851685.1		c.26C>G	p.Ser9Cys	missense	Exon 1 of 16	ENSP00000521744.1
	GNPAT	ENST00000926541.1		c.26C>G	p.Ser9Cys	missense	Exon 1 of 16	ENSP00000596600.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461710 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727200

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111848

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	8.0
DANN	Benign	0.86
DEOGEN2	Benign	0.16	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.25	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.22
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.33
MutPred		0.23		Gain of sheet (P = 0.0049)
MVP		0.69
MPC		0.22
ClinPred		0.37	T
GERP RS		-1.4
PromoterAI		-0.0048	Neutral
Varity_R		0.089
gMVP		0.32
Mutation Taster		=98/2	polymorphism

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: rs113480953; hg19: chr1-231377150;