X-14020415-G-C

Variant names:

• chrX-14020415-G-C
• rs150567066
• NM_001042479.2:c.135C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001042479.2(GEMIN8):​c.135C>G​(p.Ala45Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,204,453 control chromosomes in the GnomAD database, including 14 homozygotes. There are 521 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0076 (10 hom., 261 hem., cov: 22)
  • Exomes 𝑓: 0.00088 (4 hom. 260 hem.)
• Consequence: GEMIN8 NM_001042479.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.112
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant X-14020415-G-C is Benign according to our data. Variant chrX-14020415-G-C is described in ClinVar as [Benign]. Clinvar id is 787514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.112 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00762 (851/111734) while in subpopulation AFR AF = 0.0261 (803/30726). AF 95% confidence interval is 0.0246. There are 10 homozygotes in GnomAd4. There are 261 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GEMIN8	NM_001042479.2	c.135C>G	p.Ala45Ala	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.135C>G	p.Ala45Ala	synonymous_variant	Exon 4 of 5		NM_001042479.2	ENSP00000505429.1

Frequencies

GnomAD3 genomes AF: 0.00764 AC: 853 AN: 111681 Hom.: 10 Cov.: 22

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00322

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000941

Gnomad OTH AF: 0.00597

GnomAD2 exomes AF: 0.00219 AC: 402 AN: 183386 AF XY: 0.00146

Gnomad AFR exome AF: 0.0263

Gnomad AMR exome AF: 0.00164

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000489

Gnomad OTH exome AF: 0.000883

GnomAD4 exome AF: 0.000881 AC: 963 AN: 1092719 Hom.: 4 Cov.: 29 AF XY: 0.000726 AC XY: 260 AN XY: 358317

African (AFR) AF: 0.0282 AC: 743 AN: 26310

American (AMR) AF: 0.00196 AC: 69 AN: 35203

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19363

East Asian (EAS) AF: 0.00 AC: 0 AN: 30190

South Asian (SAS) AF: 0.000148 AC: 8 AN: 54013

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

Middle Eastern (MID) AF: 0.00194 AC: 8 AN: 4127

European-Non Finnish (NFE) AF: 0.0000418 AC: 35 AN: 837065

Other (OTH) AF: 0.00218 AC: 100 AN: 45918

GnomAD4 genome AF: 0.00762 AC: 851 AN: 111734 Hom.: 10 Cov.: 22 AF XY: 0.00769 AC XY: 261 AN XY: 33934

African (AFR) AF: 0.0261 AC: 803 AN: 30726

American (AMR) AF: 0.00322 AC: 34 AN: 10567

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3562

South Asian (SAS) AF: 0.00 AC: 0 AN: 2656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6047

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.0000941 AC: 5 AN: 53107

Other (OTH) AF: 0.00590 AC: 9 AN: 1525

Alfa AF: 0.000261 Hom.: 1

Bravo AF: 0.00925

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 19, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.52
DANN	Benign	0.54
PhyloP100		0.11
Mutation Taster		=99/1	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: rs150567066; hg19: chrX-14038534;