rs758735999

Variant names:

• chr2-43675638-C-G
• rs758735999
• NM_001101330.3:c.685G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-43675638-C-G
• chr2-43675638-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001101330.3(C1GALT1C1L):​c.685G>C​(p.Val229Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: C1GALT1C1L NM_001101330.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.886
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10547531).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101330.3. 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
	C1GALT1C1L	NM_001101330.3	MANE Select	c.685G>C	p.Val229Leu	missense	Exon 1 of 1	NP_001094800.1	P0DN25
	PLEKHH2	NM_172069.4	MANE Select	c.124-3225C>G		intron	N/A	NP_742066.2	Q8IVE3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1GALT1C1L	ENST00000475092.4	TSL:6 MANE Select	c.685G>C	p.Val229Leu	missense	Exon 1 of 1	ENSP00000489061.1	P0DN25
	PLEKHH2	ENST00000282406.9	TSL:1 MANE Select	c.124-3225C>G		intron	N/A	ENSP00000282406.4	Q8IVE3-1
	PLEKHH2	ENST00000405000.6	TSL:1	n.401-3225C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000642 AC: 16 AN: 249072 AF XY: 0.0000444

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000435

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1461508 Hom.: 0 Cov.: 41 AF XY: 0.00000963 AC XY: 7 AN XY: 727026

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.000358 AC: 16 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111822

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000413 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Benign	0.78
DEOGEN2	Benign	0.13	T
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.11	T
PhyloP100		0.89
PrimateAI	Benign	0.36	T
Sift4G	Uncertain	0.020	D
Vest4		0.37
GERP RS		0.80
Varity_R		0.077
gMVP		0.64
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs758735999; hg19: chr2-43902777;