3-52695520-G-C

Variant names:

• chr3-52695520-G-C
• NM_018446.4:c.713C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018446.4(GLT8D1):​c.713C>G​(p.Thr238Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,106 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GLT8D1 NM_018446.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.54
• Publications: 0 publications found

Genes affected

GLT8D1 (HGNC:24870): (glycosyltransferase 8 domain containing 1) This gene encodes a member of the glycosyltransferase family. The specific function of this protein has not been determined. Alternative splicing results in multiple transcript variants of this gene [provided by RefSeq, May 2013]

GNL3 (HGNC:29931): (G protein nucleolar 3) The protein encoded by this gene may interact with p53 and may be involved in tumorigenesis. The encoded protein also appears to be important for stem cell proliferation. This protein is found in both the nucleus and nucleolus. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018446.4. 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
	GLT8D1	NM_018446.4	MANE Select	c.713C>G	p.Thr238Ser	missense	Exon 8 of 10	NP_060916.1	Q68CQ7-1
	GLT8D1	NM_001010983.3		c.713C>G	p.Thr238Ser	missense	Exon 9 of 11	NP_001010983.1	Q68CQ7-1
	GLT8D1	NM_001278280.2		c.713C>G	p.Thr238Ser	missense	Exon 9 of 11	NP_001265209.1	Q68CQ7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLT8D1	ENST00000266014.11	TSL:1 MANE Select	c.713C>G	p.Thr238Ser	missense	Exon 8 of 10	ENSP00000266014.5	Q68CQ7-1
	GLT8D1	ENST00000394783.7	TSL:1	c.713C>G	p.Thr238Ser	missense	Exon 8 of 10	ENSP00000378263.3	Q68CQ7-1
	GLT8D1	ENST00000478968.6	TSL:1	c.713C>G	p.Thr238Ser	missense	Exon 9 of 11	ENSP00000419612.2	Q68CQ7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459106 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726084

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109506

Other (OTH) AF: 0.00 AC: 0 AN: 60294

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Amyotrophic lateral sclerosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		9.5
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.24
Sift	Uncertain	0.014	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.59
MutPred		0.40		Gain of disorder (P = 0.0266)
MVP		0.73
ClinPred		0.96	D
GERP RS		5.8
Varity_R		0.52
gMVP		0.62
Mutation Taster		=46/54	disease causing

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

hg19: chr3-52729536;