rs1207197177

Variant names:

• chr3-52695550-C-A
• rs1207197177
• NM_018446.4:c.683G>T

Variant summary

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

The NM_018446.4(GLT8D1):​c.683G>T​(p.Arg228Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,458,534 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: 0.0000021 (0 hom.)
• Consequence: GLT8D1 NM_018446.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.36
• 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.683G>T	p.Arg228Ile	missense	Exon 8 of 10	NP_060916.1	Q68CQ7-1
	GLT8D1	NM_001010983.3		c.683G>T	p.Arg228Ile	missense	Exon 9 of 11	NP_001010983.1	Q68CQ7-1
	GLT8D1	NM_001278280.2		c.683G>T	p.Arg228Ile	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.683G>T	p.Arg228Ile	missense	Exon 8 of 10	ENSP00000266014.5	Q68CQ7-1
	GLT8D1	ENST00000394783.7	TSL:1	c.683G>T	p.Arg228Ile	missense	Exon 8 of 10	ENSP00000378263.3	Q68CQ7-1
	GLT8D1	ENST00000478968.6	TSL:1	c.683G>T	p.Arg228Ile	missense	Exon 9 of 11	ENSP00000419612.2	Q68CQ7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251088 AF XY: 0.00000737

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458534 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725800

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109028

Other (OTH) AF: 0.0000166 AC: 1 AN: 60274

GnomAD4 genome Cov.: 32

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	0.17
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.51	D
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0094	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		4.4
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.14
Sift	Benign	0.10	T
Sift4G	Benign	0.18	T
Polyphen		0.80	P
Vest4		0.56
MutPred		0.59		Loss of MoRF binding (P = 0.0248)
MVP		0.30
ClinPred		0.76	D
GERP RS		5.0
Varity_R		0.22
gMVP		0.65
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1207197177; hg19: chr3-52729566;