2-43675638-C-T

Variant summary

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

The NM_001101330.3(C1GALT1C1L):​c.685G>A​(p.Val229Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/12 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. V229L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

C1GALT1C1L
NM_001101330.3 missense

Scores

10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.886
Variant links:
Genes affected
C1GALT1C1L (HGNC:51617): (C1GALT1 specific chaperone 1 like) Predicted to enable glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase activity. Predicted to be involved in O-glycan processing, core 1. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
PLEKHH2 (HGNC:30506): (pleckstrin homology, MyTH4 and FERM domain containing H2) Predicted to enable actin binding activity. Predicted to be involved in negative regulation of actin filament depolymerization. Located in several cellular components, including cytosol; lamellipodium; and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

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=0.08479419).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C1GALT1C1LNM_001101330.3 linkc.685G>A p.Val229Ile missense_variant Exon 1 of 1 ENST00000475092.4 NP_001094800.1 P0DN25
PLEKHH2NM_172069.4 linkc.124-3225C>T intron_variant Intron 2 of 29 ENST00000282406.9 NP_742066.2 Q8IVE3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C1GALT1C1LENST00000475092.4 linkc.685G>A p.Val229Ile missense_variant Exon 1 of 1 6 NM_001101330.3 ENSP00000489061.1 P0DN25
PLEKHH2ENST00000282406.9 linkc.124-3225C>T intron_variant Intron 2 of 29 1 NM_172069.4 ENSP00000282406.4 Q8IVE3-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000803
AC:
2
AN:
249072
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135118
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461508
Hom.:
0
Cov.:
41
AF XY:
0.00000138
AC XY:
1
AN XY:
727026
show subpopulations
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000827
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_noAF
Benign
-0.44
CADD
Benign
16
DANN
Benign
0.75
DEOGEN2
Benign
0.034
T
FATHMM_MKL
Benign
0.58
D
LIST_S2
Benign
0.80
T
MetaRNN
Benign
0.085
T
PrimateAI
Benign
0.30
T
Sift4G
Benign
0.099
T
Vest4
0.11
GERP RS
0.80
Varity_R
0.043
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs758735999; hg19: chr2-43902777; API