rs121434424

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001492.6(GDF1):​c.485G>T​(p.Gly162Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000665 in 150,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. G162D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

GDF1
NM_001492.6 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0550
Variant links:
Genes affected
GDF1 (HGNC:4214): (growth differentiation factor 1) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. Studies in rodents suggest that this protein is involved in the establishment of left-right asymmetry in early embryogenesis and in neural development in later embryogenesis. The encoded protein is translated from a bicistronic mRNA that also encodes ceramide synthase 1. Mutations in this gene are associated with several congenital cardiovascular malformations. [provided by RefSeq, Jul 2016]
CERS1 (HGNC:14253): (ceramide synthase 1) This gene encodes a ceramide synthase enzyme, which catalyzes the synthesis of ceramide, the hydrophobic moiety of sphingolipids. The encoded enzyme synthesizes 18-carbon (C18) ceramide in brain neurons. Elevated expression of this gene may be associated with increased longevity, while decreased expression of this gene may be associated with myoclonus epilepsy with dementia in human patients. This protein is transcribed from a monocistronic mRNA as well as a bicistronic mRNA, which also encodes growth differentiation factor 1. [provided by RefSeq, Jul 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26075703).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GDF1NM_001492.6 linkuse as main transcriptc.485G>T p.Gly162Val missense_variant 8/8 ENST00000247005.8 NP_001483.3
CERS1NM_021267.5 linkuse as main transcriptc.*754G>T 3_prime_UTR_variant 8/8 ENST00000623882.4 NP_067090.1
GDF1NM_001387438.1 linkuse as main transcriptc.485G>T p.Gly162Val missense_variant 5/5 NP_001374367.1
CERS1NM_001387440.1 linkuse as main transcriptc.*1346G>T 3_prime_UTR_variant 7/7 NP_001374369.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GDF1ENST00000247005.8 linkuse as main transcriptc.485G>T p.Gly162Val missense_variant 8/81 NM_001492.6 ENSP00000247005 P1
CERS1ENST00000623882.4 linkuse as main transcriptc.*754G>T 3_prime_UTR_variant 8/81 NM_021267.5 ENSP00000485308 P2P27544-1

Frequencies

GnomAD3 genomes
AF:
0.00000665
AC:
1
AN:
150336
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1238690
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
606732
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000665
AC:
1
AN:
150336
Hom.:
0
Cov.:
33
AF XY:
0.0000136
AC XY:
1
AN XY:
73356
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.082
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
19
DANN
Benign
0.97
DEOGEN2
Benign
0.12
T;.
Eigen
Benign
-0.50
Eigen_PC
Benign
-0.55
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.42
T;.
M_CAP
Pathogenic
0.76
D
MetaRNN
Benign
0.26
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;.
MutationTaster
Benign
1.0
D;D
PROVEAN
Benign
-0.46
N;.
REVEL
Benign
0.084
Sift
Benign
0.26
T;.
Sift4G
Benign
0.42
T;T
Vest4
0.14
MutPred
0.47
Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP
0.21
MPC
2.2
ClinPred
0.45
T
GERP RS
2.1
Varity_R
0.082
gMVP
0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs121434424; hg19: chr19-18980040; API