chr17-744917-G-A

Variant names:

• chr17-744917-G-A
• rs1045481
• NM_015721.3:c.3126C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_015721.3(GEMIN4):​c.3126C>T​(p.Ile1042Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,613,264 control chromosomes in the GnomAD database, including 46,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.19 (3261 hom., cov: 34)
  • Exomes 𝑓: 0.24 (43381 hom.)
• Consequence: GEMIN4 NM_015721.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.235

Genes affected

GEMIN4 (HGNC:15717): (gem nuclear organelle associated protein 4) The product of this gene is part of a large complex localized to the cytoplasm, nucleoli, and to discrete nuclear bodies called Gemini bodies (gems). The complex functions in spliceosomal snRNP assembly in the cytoplasm, and regenerates spliceosomes required for pre-mRNA splicing in the nucleus. The encoded protein directly interacts with a DEAD box protein and several spliceosome core proteins. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-744917-G-A is Benign according to our data. Variant chr17-744917-G-A is described in ClinVar as [Benign]. Clinvar id is 3057158.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.235 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GEMIN4	NM_015721.3	c.3126C>T	p.Ile1042Ile	synonymous_variant	Exon 2 of 2	ENST00000319004.6	NP_056536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GEMIN4	ENST00000319004.6	c.3126C>T	p.Ile1042Ile	synonymous_variant	Exon 2 of 2	1	NM_015721.3	ENSP00000321706.5
GEMIN4	ENST00000576778.1	c.3093C>T	p.Ile1031Ile	synonymous_variant	Exon 1 of 1	6		ENSP00000459565.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29026 AN: 152152 Hom.: 3259 Cov.: 34

Gnomad AFR AF: 0.0909

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.209

GnomAD2 exomes AF: 0.204 AC: 50474 AN: 247916 AF XY: 0.208

Gnomad AFR exome AF: 0.0906

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.246

Gnomad EAS exome AF: 0.114

Gnomad FIN exome AF: 0.193

Gnomad NFE exome AF: 0.258

Gnomad OTH exome AF: 0.215

GnomAD4 exome AF: 0.239 AC: 349395 AN: 1460994 Hom.: 43381 Cov.: 32 AF XY: 0.238 AC XY: 173113 AN XY: 726764

Gnomad4 AFR exome AF: 0.0854 AC: 2858 AN: 33468

Gnomad4 AMR exome AF: 0.125 AC: 5584 AN: 44678

Gnomad4 ASJ exome AF: 0.244 AC: 6357 AN: 26106

Gnomad4 EAS exome AF: 0.145 AC: 5747 AN: 39692

Gnomad4 SAS exome AF: 0.194 AC: 16697 AN: 86180

Gnomad4 FIN exome AF: 0.191 AC: 10202 AN: 53310

Gnomad4 NFE exome AF: 0.258 AC: 287154 AN: 1111562

Gnomad4 Remaining exome AF: 0.232 AC: 13981 AN: 60322

GnomAD4 genome AF: 0.191 AC: 29033 AN: 152270 Hom.: 3261 Cov.: 34 AF XY: 0.189 AC XY: 14066 AN XY: 74464

Gnomad4 AFR AF: 0.0907 AC: 0.0907429 AN: 0.0907429

Gnomad4 AMR AF: 0.159 AC: 0.158797 AN: 0.158797

Gnomad4 ASJ AF: 0.244 AC: 0.243664 AN: 0.243664

Gnomad4 EAS AF: 0.125 AC: 0.124759 AN: 0.124759

Gnomad4 SAS AF: 0.219 AC: 0.219462 AN: 0.219462

Gnomad4 FIN AF: 0.189 AC: 0.188633 AN: 0.188633

Gnomad4 NFE AF: 0.256 AC: 0.256417 AN: 0.256417

Gnomad4 OTH AF: 0.207 AC: 0.207386 AN: 0.207386

Alfa AF: 0.225 Hom.: 7475

Bravo AF: 0.184

Asia WGS AF: 0.188 AC: 658 AN: 3478

EpiCase AF: 0.248

EpiControl AF: 0.251

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

GEMIN4-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.12
DANN	Benign	0.85
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

Publications

LitVar

Other links and lift over

dbSNP: rs1045481; hg19: chr17-648157; COSMIC: COSV56744812; COSMIC: COSV56744812;