3-52694933-G-C

Variant names:

• chr3-52694933-G-C
• rs147971167
• NM_018446.4:c.1028C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018446.4(GLT8D1):​c.1028C>G​(p.Thr343Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T343I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GLT8D1 NM_018446.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.30
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048612326).

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.1028C>G	p.Thr343Ser	missense	Exon 10 of 10	NP_060916.1	Q68CQ7-1
	GLT8D1	NM_001010983.3		c.1028C>G	p.Thr343Ser	missense	Exon 11 of 11	NP_001010983.1	Q68CQ7-1
	GLT8D1	NM_001278280.2		c.1028C>G	p.Thr343Ser	missense	Exon 11 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.1028C>G	p.Thr343Ser	missense	Exon 10 of 10	ENSP00000266014.5	Q68CQ7-1
	GLT8D1	ENST00000394783.7	TSL:1	c.1028C>G	p.Thr343Ser	missense	Exon 10 of 10	ENSP00000378263.3	Q68CQ7-1
	GLT8D1	ENST00000478968.6	TSL:1	c.1028C>G	p.Thr343Ser	missense	Exon 11 of 11	ENSP00000419612.2	Q68CQ7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457314 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725440

African (AFR) AF: 0.00 AC: 0 AN: 33370

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107866

Other (OTH) AF: 0.00 AC: 0 AN: 60234

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.6
DANN	Benign	0.73
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.67
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.090	N
PhyloP100		4.3
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.061
Sift	Benign	0.57	T
Sift4G	Benign	0.61	T
Polyphen		0.0	B
Vest4		0.040
MutPred		0.28		Gain of helix (P = 0.0854)
MVP		0.26
ClinPred		0.12	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.034
gMVP		0.34
Mutation Taster		=94/6	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: rs147971167; hg19: chr3-52728949;