Variant chr2-43675415-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001101330.3(C1GALT1C1L):c.908C>T(p.Thr303Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,454,650 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

C1GALT1C1L
NM_001101330.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.91

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]

C1GALT1C1L links:

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]

PLEKHH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058906883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1GALT1C1L	NM_001101330.3 linkuse as main transcript	c.908C>T	p.Thr303Ile	missense_variant	1/1	ENST00000475092.4
PLEKHH2	NM_172069.4 linkuse as main transcript	c.124-3448G>A		intron_variant		ENST00000282406.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1GALT1C1L	ENST00000475092.4 linkuse as main transcript	c.908C>T	p.Thr303Ile	missense_variant	1/1		NM_001101330.3	P1
PLEKHH2	ENST00000282406.9 linkuse as main transcript	c.124-3448G>A		intron_variant		1	NM_172069.4	P1	Q8IVE3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000538

AC:

AN:

241842

Hom.:

AF XY:

0.0000763

AC XY:

AN XY:

131006

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:

0.000454

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000254

AC:

AN:

1454650

Hom.:

Cov.:

AF XY:

0.0000387

AC XY:

AN XY:

723112

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:

0.000438

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000579

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 22, 2024

The c.908C>T (p.T303I) alteration is located in exon 1 (coding exon 1) of the C1GALT1C1L gene. This alteration results from a C to T substitution at nucleotide position 908, causing the threonine (T) at amino acid position 303 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.025

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.60

MetaRNN

Benign

0.059

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

Sift4G

Benign

0.35

Vest4

0.052

GERP RS

0.67

Varity_R

0.050

gMVP

0.17

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over