rs370925278

Variant names:

• chr2-43675584-G-T
• rs370925278
• NM_001101330.3:c.739C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-43675584-G-T
• chr2-43675584-G-A
• chr2-43675584-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001101330.3(C1GALT1C1L):​c.739C>A​(p.Pro247Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,613,640 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.000092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: C1GALT1C1L NM_001101330.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.24
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.031959265).

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.739C>A	p.Pro247Thr	missense	Exon 1 of 1	NP_001094800.1	P0DN25
	PLEKHH2	NM_172069.4	MANE Select	c.124-3279G>T		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.739C>A	p.Pro247Thr	missense	Exon 1 of 1	ENSP00000489061.1	P0DN25
	PLEKHH2	ENST00000282406.9	TSL:1 MANE Select	c.124-3279G>T		intron	N/A	ENSP00000282406.4	Q8IVE3-1
	PLEKHH2	ENST00000405000.6	TSL:1	n.401-3279G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152152 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000173 AC: 43 AN: 248732 AF XY: 0.000245

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000581

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.000204

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000116 AC: 169 AN: 1461370 Hom.: 1 Cov.: 39 AF XY: 0.000136 AC XY: 99 AN XY: 726950

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.0000447 AC: 2 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000476 AC: 41 AN: 86142

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53396

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5766

European-Non Finnish (NFE) AF: 0.0000962 AC: 107 AN: 1111726

Other (OTH) AF: 0.000133 AC: 8 AN: 60362

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152270 Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5 AN XY: 74464

African (AFR) AF: 0.00 AC: 0 AN: 41544

American (AMR) AF: 0.000131 AC: 2 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000114 Hom.: 0

Bravo AF: 0.000102

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000165 AC: 20

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	0.13
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.67
DEOGEN2	Benign	0.069	T
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.032	T
PhyloP100		1.2
PrimateAI	Benign	0.34	T
Sift4G	Benign	0.66	T
Vest4		0.062
GERP RS		2.5
Varity_R		0.054
gMVP		0.30
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs370925278; hg19: chr2-43902723;