chr3-52695182-C-CTACT

Variant names:

• chr3-52695182-C-CTACT
• rs60069075
• NM_018446.4:c.925+4_925+7dupAGTA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_018446.4(GLT8D1):​c.925+4_925+7dupAGTA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 1,589,536 control chromosomes in the GnomAD database, including 328 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.015 (21 hom., cov: 32)
  • Exomes 𝑓: 0.019 (307 hom.)
• Consequence: GLT8D1 NM_018446.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.015 (2292/152306) while in subpopulation SAS AF = 0.036 (174/4828). AF 95% confidence interval is 0.0317. There are 21 homozygotes in GnomAd4. There are 1117 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2292 AD gene.

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.925+4_925+7dupAGTA		splice_region intron	N/A	NP_060916.1	Q68CQ7-1
	GLT8D1	NM_001010983.3		c.925+4_925+7dupAGTA		splice_region intron	N/A	NP_001010983.1	Q68CQ7-1
	GLT8D1	NM_001278280.2		c.925+4_925+7dupAGTA		splice_region intron	N/A	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.925+4_925+7dupAGTA		splice_region intron	N/A	ENSP00000266014.5	Q68CQ7-1
	GLT8D1	ENST00000394783.7	TSL:1	c.925+4_925+7dupAGTA		splice_region intron	N/A	ENSP00000378263.3	Q68CQ7-1
	GLT8D1	ENST00000478968.6	TSL:1	c.925+4_925+7dupAGTA		splice_region intron	N/A	ENSP00000419612.2	Q68CQ7-1

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2289 AN: 152188 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.00721

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0208

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0356

Gnomad FIN AF: 0.00575

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0196

Gnomad OTH AF: 0.0224

GnomAD2 exomes AF: 0.0161 AC: 4019 AN: 249460 AF XY: 0.0175

Gnomad AFR exome AF: 0.00776

Gnomad AMR exome AF: 0.0110

Gnomad ASJ exome AF: 0.0134

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00671

Gnomad NFE exome AF: 0.0187

Gnomad OTH exome AF: 0.0184

GnomAD4 exome AF: 0.0188 AC: 26962 AN: 1437230 Hom.: 307 Cov.: 28 AF XY: 0.0193 AC XY: 13794 AN XY: 716510

African (AFR) AF: 0.00915 AC: 302 AN: 32996

American (AMR) AF: 0.0113 AC: 502 AN: 44474

Ashkenazi Jewish (ASJ) AF: 0.0145 AC: 375 AN: 25782

East Asian (EAS) AF: 0.000152 AC: 6 AN: 39596

South Asian (SAS) AF: 0.0350 AC: 2998 AN: 85578

European-Finnish (FIN) AF: 0.00604 AC: 322 AN: 53320

Middle Eastern (MID) AF: 0.0212 AC: 121 AN: 5708

European-Non Finnish (NFE) AF: 0.0195 AC: 21283 AN: 1090286

Other (OTH) AF: 0.0177 AC: 1053 AN: 59490

GnomAD4 genome AF: 0.0150 AC: 2292 AN: 152306 Hom.: 21 Cov.: 32 AF XY: 0.0150 AC XY: 1117 AN XY: 74480

African (AFR) AF: 0.00724 AC: 301 AN: 41586

American (AMR) AF: 0.0207 AC: 317 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0360 AC: 174 AN: 4828

European-Finnish (FIN) AF: 0.00575 AC: 61 AN: 10608

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0196 AC: 1334 AN: 68016

Other (OTH) AF: 0.0227 AC: 48 AN: 2116

Alfa AF: 0.0169 Hom.: 8

Bravo AF: 0.0148

Asia WGS AF: 0.0140 AC: 50 AN: 3478

EpiCase AF: 0.0170

EpiControl AF: 0.0177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs60069075; hg19: chr3-52729198;