1-231241404-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014236.4(GNPAT):​c.26C>T​(p.Ser9Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 1,613,988 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (61 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (65 hom.)
• Consequence: GNPAT NM_014236.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.223
• Publications: 4 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020586848).
• BP6: Variant 1-231241404-C-T is Benign according to our data. Variant chr1-231241404-C-T is described in ClinVar as Benign. ClinVar VariationId is 260361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

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>T	p.Ser9Phe	missense	Exon 1 of 16	NP_055051.1	O15228-1
	GNPAT	NM_001316350.2		c.26C>T	p.Ser9Phe	missense	Exon 1 of 15	NP_001303279.1	O15228-2
	FSAF1	NM_152379.4	MANE Select	c.-263G>A		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.26C>T	p.Ser9Phe	missense	Exon 1 of 16	ENSP00000355607.4	O15228-1
	GNPAT	ENST00000851685.1		c.26C>T	p.Ser9Phe	missense	Exon 1 of 16	ENSP00000521744.1
	GNPAT	ENST00000926541.1		c.26C>T	p.Ser9Phe	missense	Exon 1 of 16	ENSP00000596600.1

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2443 AN: 152178 Hom.: 60 Cov.: 33

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00422 AC: 1052 AN: 249172 AF XY: 0.00297

Gnomad AFR exome AF: 0.0567

Gnomad AMR exome AF: 0.00301

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000987

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00154 AC: 2252 AN: 1461692 Hom.: 65 Cov.: 31 AF XY: 0.00129 AC XY: 938 AN XY: 727190

African (AFR) AF: 0.0545 AC: 1824 AN: 33458

American (AMR) AF: 0.00306 AC: 137 AN: 44724

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86252

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

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.0000513 AC: 57 AN: 1111848

Other (OTH) AF: 0.00338 AC: 204 AN: 60394

GnomAD4 genome AF: 0.0162 AC: 2467 AN: 152296 Hom.: 61 Cov.: 33 AF XY: 0.0157 AC XY: 1172 AN XY: 74472

African (AFR) AF: 0.0563 AC: 2339 AN: 41558

American (AMR) AF: 0.00647 AC: 99 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68014

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.00581 Hom.: 35

Bravo AF: 0.0186

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0486 AC: 214

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00534 AC: 648

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000296

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	2	Rhizomelic chondrodysplasia punctata type 2 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.18	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.22
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.31
MVP		0.63
MPC		0.25
ClinPred		0.030	T
GERP RS		-1.4
PromoterAI		-0.099	Neutral
Varity_R		0.066
gMVP		0.36
Mutation Taster		=99/1	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;