rs772792622

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-14020382-T-A
• chrX-14020382-T-C
• chrX-14020382-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001042479.2(GEMIN8):​c.168A>T​(p.Leu56Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,209,290 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: GEMIN8 NM_001042479.2 missense
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.025341094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GEMIN8	NM_001042479.2	c.168A>T	p.Leu56Phe	missense_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>T	p.Leu56Phe	missense_variant	Exon 4 of 5		NM_001042479.2	ENSP00000505429.1

Frequencies

GnomAD3 genomes AF: 0.00000893 AC: 1 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: 0.000279

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097291 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 AN: 30201

South Asian (SAS) AF: 0.00 AC: 0 AN: 54124

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 841281

Other (OTH) AF: 0.00 AC: 0 AN: 46056

GnomAD4 genome AF: 0.00000893 AC: 1 AN: 111999 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34157

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

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: 0.000279 AC: 1 AN: 3590

South Asian (SAS) AF: 0.00 AC: 0 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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.31
DANN	Benign	0.052
DEOGEN2	Benign	0.0047	T;T;T
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.23	.;T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.025	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.1	N;N;.
PhyloP100		0.30
PrimateAI	Benign	0.24	T
PROVEAN	Benign	1.4	N;N;N
REVEL	Benign	0.070
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.99	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.057
MutPred		0.23		Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);
MVP		0.043
MPC		0.38
ClinPred		0.061	T
GERP RS		0.29
Varity_R		0.066
gMVP		0.10
Mutation Taster		=97/3	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;