rs6976

Variant names:

• chr3-52694788-C-T
• rs6976
• NM_018446.4:c.*57G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018446.4(GLT8D1):​c.*57G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,185,854 control chromosomes in the GnomAD database, including 86,465 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (9497 hom., cov: 33)
  • Exomes 𝑓: 0.38 (76968 hom.)
• Consequence: GLT8D1 NM_018446.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.423
• Publications: 76 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.014).
• BP6: Variant 3-52694788-C-T is Benign according to our data. Variant chr3-52694788-C-T is described in ClinVar as Benign. ClinVar VariationId is 1224650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

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.*57G>A		3_prime_UTR	Exon 10 of 10	NP_060916.1	Q68CQ7-1
	GLT8D1	NM_001010983.3		c.*57G>A		3_prime_UTR	Exon 11 of 11	NP_001010983.1	Q68CQ7-1
	GLT8D1	NM_001278280.2		c.*57G>A		3_prime_UTR	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.*57G>A		3_prime_UTR	Exon 10 of 10	ENSP00000266014.5	Q68CQ7-1
	GLT8D1	ENST00000394783.7	TSL:1	c.*57G>A		3_prime_UTR	Exon 10 of 10	ENSP00000378263.3	Q68CQ7-1
	GLT8D1	ENST00000478968.6	TSL:1	c.*57G>A		3_prime_UTR	Exon 11 of 11	ENSP00000419612.2	Q68CQ7-1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50272 AN: 152050 Hom.: 9494 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.357

GnomAD2 exomes AF: 0.382 AC: 93099 AN: 243900 AF XY: 0.373

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.530

Gnomad ASJ exome AF: 0.450

Gnomad EAS exome AF: 0.426

Gnomad FIN exome AF: 0.404

Gnomad NFE exome AF: 0.400

Gnomad OTH exome AF: 0.381

GnomAD4 exome AF: 0.378 AC: 390224 AN: 1033686 Hom.: 76968 Cov.: 14 AF XY: 0.371 AC XY: 197900 AN XY: 533282

African (AFR) AF: 0.141 AC: 3579 AN: 25370

American (AMR) AF: 0.516 AC: 22524 AN: 43620

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 10706 AN: 23326

East Asian (EAS) AF: 0.479 AC: 18084 AN: 37768

South Asian (SAS) AF: 0.208 AC: 16149 AN: 77476

European-Finnish (FIN) AF: 0.401 AC: 20655 AN: 51544

Middle Eastern (MID) AF: 0.399 AC: 1981 AN: 4960

European-Non Finnish (NFE) AF: 0.387 AC: 279942 AN: 723168

Other (OTH) AF: 0.357 AC: 16604 AN: 46454

GnomAD4 genome AF: 0.331 AC: 50296 AN: 152168 Hom.: 9497 Cov.: 33 AF XY: 0.333 AC XY: 24739 AN XY: 74366

African (AFR) AF: 0.149 AC: 6197 AN: 41540

American (AMR) AF: 0.457 AC: 6985 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1560 AN: 3472

East Asian (EAS) AF: 0.427 AC: 2214 AN: 5182

South Asian (SAS) AF: 0.208 AC: 1002 AN: 4828

European-Finnish (FIN) AF: 0.391 AC: 4129 AN: 10556

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26900 AN: 67978

Other (OTH) AF: 0.362 AC: 765 AN: 2114

Alfa AF: 0.370 Hom.: 23219

Bravo AF: 0.330

Asia WGS AF: 0.330 AC: 1146 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.63
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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: rs6976; hg19: chr3-52728804; COSMIC: COSV56476954; COSMIC: COSV56476954;