X-14020382-T-C

Variant names:

• chrX-14020382-T-C
• rs772792622
• NM_001042479.2:c.168A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001042479.2(GEMIN8):​c.168A>G​(p.Leu56Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000703 in 1,209,290 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 29 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., 4 hem., cov: 23)
  • Exomes 𝑓: 0.000067 (0 hom. 25 hem.)
• Consequence: GEMIN8 NM_001042479.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 0 publications found

Genes affected

GEMIN8 (HGNC:26044): (gem nuclear organelle associated protein 8) The protein encoded by this gene is part of the SMN complex, which is necessary for spliceosomal snRNP assembly in the cytoplasm and pre-mRNA splicing in the nucleus. The encoded protein binds to both SMN1 and the GEMIN6/GEMIN7 heterodimer, mediating their interaction. This protein is found in nuclear Gemini of Cajal bodies (gems) and in the cytoplasm. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=0.299 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GEMIN8	NM_001042479.2	c.168A>G	p.Leu56Leu	synonymous_variant	Exon 4 of 5	ENST00000680255.1	NP_001035944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GEMIN8	ENST00000680255.1	c.168A>G	p.Leu56Leu	synonymous_variant	Exon 4 of 5		NM_001042479.2	ENSP00000505429.1

Frequencies

GnomAD3 genomes AF: 0.000107 AC: 12 AN: 111999 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.00111

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000240 AC: 44 AN: 183374 AF XY: 0.000177

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00289

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.0000665 AC: 73 AN: 1097291 Hom.: 0 Cov.: 29 AF XY: 0.0000689 AC XY: 25 AN XY: 362653

African (AFR) AF: 0.00 AC: 0 AN: 26383

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19376

East Asian (EAS) AF: 0.00132 AC: 40 AN: 30201

South Asian (SAS) AF: 0.000333 AC: 18 AN: 54124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40530

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4133

European-Non Finnish (NFE) AF: 0.00000357 AC: 3 AN: 841281

Other (OTH) AF: 0.000239 AC: 11 AN: 46056

GnomAD4 genome AF: 0.000107 AC: 12 AN: 111999 Hom.: 0 Cov.: 23 AF XY: 0.000117 AC XY: 4 AN XY: 34157

African (AFR) AF: 0.00 AC: 0 AN: 30750

American (AMR) AF: 0.00 AC: 0 AN: 10592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00251 AC: 9 AN: 3590

South Asian (SAS) AF: 0.00111 AC: 3 AN: 2706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53176

Other (OTH) AF: 0.00 AC: 0 AN: 1513

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000125

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.33
PhyloP100		0.30
Mutation Taster		=100/0	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: rs772792622; hg19: chrX-14038501;