1-231241060-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152379.4(FSAF1):c.82C>G(p.Leu28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 1,614,004 control chromosomes in the GnomAD database, including 8,455 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 682 hom., cov: 33)

Exomes 𝑓: 0.099 ( 7773 hom. )

Consequence

FSAF1
NM_152379.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.14

Publications

27 publications found

Variant links:

Genes affected

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

FSAF1 links:

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)

GNPAT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.944141E-4).

BP6

Variant 1-231241060-G-C is Benign according to our data. Variant chr1-231241060-G-C is described in ClinVar as Benign. ClinVar VariationId is 1266325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152379.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FSAF1	NM_152379.4	MANE Select	c.82C>G	p.Leu28Val	missense	Exon 1 of 7	NP_689592.2
FSAF1	NM_001300830.2		c.82C>G	p.Leu28Val	missense	Exon 1 of 7	NP_001287759.1
GNPAT	NM_014236.4	MANE Select	c.-319G>C		upstream_gene	N/A	NP_055051.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FSAF1	ENST00000366649.7	TSL:1 MANE Select	c.82C>G	p.Leu28Val	missense	Exon 1 of 7	ENSP00000355609.2
FSAF1	ENST00000366651.7	TSL:1	c.82C>G	p.Leu28Val	missense	Exon 1 of 7	ENSP00000355611.3
FSAF1	ENST00000318906.6	TSL:1	c.82C>G	p.Leu28Val	missense	Exon 1 of 6	ENSP00000321341.2

Frequencies

GnomAD3 genomes

AF:

0.0844

AC:

12846

AN:

152200

Hom.:

683

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0471

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.0818

Gnomad EAS

AF:

0.0897

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.0530

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0927

Gnomad OTH

AF:

0.0759

GnomAD2 exomes

AF:

0.107

AC:

26824

AN:

251406

AF XY:

0.105

show subpopulations

Gnomad AFR exome

AF:

0.0447

Gnomad AMR exome

AF:

0.220

Gnomad ASJ exome

AF:

0.0807

Gnomad EAS exome

AF:

0.0798

Gnomad FIN exome

AF:

0.0570

Gnomad NFE exome

AF:

0.0935

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.0987

AC:

144287

AN:

1461686

Hom.:

7773

Cov.:

AF XY:

0.0987

AC XY:

71805

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.0417

AC:

1396

AN:

33472

American (AMR)

AF:

0.214

AC:

9566

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0770

AC:

2013

AN:

26136

East Asian (EAS)

AF:

0.0942

AC:

3739

AN:

39700

South Asian (SAS)

AF:

0.121

AC:

10401

AN:

86246

European-Finnish (FIN)

AF:

0.0567

AC:

3028

AN:

53418

Middle Eastern (MID)

AF:

0.0716

AC:

413

AN:

5766

European-Non Finnish (NFE)

AF:

0.0974

AC:

108282

AN:

1111842

Other (OTH)

AF:

0.0902

AC:

5449

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

6974

13947

20921

27894

34868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4082

8164

12246

16328

20410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0844

AC:

12849

AN:

152318

Hom.:

682

Cov.:

AF XY:

0.0837

AC XY:

6237

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.0470

AC:

1953

AN:

41568

American (AMR)

AF:

0.161

AC:

2466

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0818

AC:

284

AN:

3472

East Asian (EAS)

AF:

0.0899

AC:

465

AN:

5174

South Asian (SAS)

AF:

0.116

AC:

559

AN:

4830

European-Finnish (FIN)

AF:

0.0530

AC:

563

AN:

10622

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0927

AC:

6304

AN:

68028

Other (OTH)

AF:

0.0751

AC:

159

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

599

1198

1796

2395

2994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

312

468

624

780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0819

Hom.:

484

Bravo

AF:

0.0890

TwinsUK

AF:

0.0947

AC:

351

ALSPAC

AF:

0.102

AC:

394

ESP6500AA

AF:

0.0477

AC:

210

ESP6500EA

AF:

0.103

AC:

888

ExAC

AF:

0.102

AC:

12432

Asia WGS

AF:

0.100

AC:

350

AN:

3478

EpiCase

AF:

0.0947

EpiControl

AF:

0.0928

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

Eigen

Benign

0.084

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.77

MetaRNN

Benign

0.00099

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

3.1

PROVEAN

Benign

-1.6

REVEL

Benign

0.080

Sift

Uncertain

0.017

Sift4G

Benign

0.078

Polyphen

1.0

Vest4

0.14

MPC

0.26

ClinPred

0.072

GERP RS

3.1

PromoterAI

-0.00080

Neutral

(source)

Varity_R

0.20

gMVP

0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over