rs1056104

chr2-38781807-G-Achr2-38781807-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024775.10(GEMIN6):c.419G>A(p.Gly140Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0827 in 1,613,982 control chromosomes in the GnomAD database, including 7,472 homozygotes. In-silico tool predicts 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.070 (575 hom., cov: 31)
  • Exomes 𝑓: 0.084 (6897 hom.)
• Consequence: GEMIN6 NM_024775.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.05

Genes affected

GEMIN6 (HGNC:20044): (gem nuclear organelle associated protein 6) GEMIN6 is part of a large macromolecular complex, localized to both the cytoplasm and the nucleus, that plays a role in the cytoplasmic assembly of small nuclear ribonucleoproteins (snRNPs). Other members of this complex include SMN (MIM 600354), GEMIN2 (SIP1; MIM 602595), GEMIN3 (DDX20; MIM 606168), GEMIN4 (MIM 606969), and GEMIN5 (MIM 607005).[supplied by OMIM, Jul 2002]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015923977).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GEMIN6	NM_024775.10	c.419G>A	p.Gly140Asp	missense_variant	3/3	ENST00000281950.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GEMIN6	ENST00000281950.8	c.419G>A	p.Gly140Asp	missense_variant	3/3	1	NM_024775.10	P1
GEMIN6	ENST00000409011.5	c.*277G>A		3_prime_UTR_variant	6/6	1
GEMIN6	ENST00000409566.1	c.*267G>A		3_prime_UTR_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 10685 AN: 152040 Hom.: 575 Cov.: 31

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0970

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0513

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0748

Gnomad OTH AF: 0.0761

GnomAD3 exomes AF: 0.104 AC: 26112 AN: 251324 Hom.: 1928 AF XY: 0.106 AC XY: 14398 AN XY: 135824

Gnomad AFR exome AF: 0.0129

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.295

Gnomad SAS exome AF: 0.153

Gnomad FIN exome AF: 0.0537

Gnomad NFE exome AF: 0.0755

Gnomad OTH exome AF: 0.105

GnomAD4 exome AF: 0.0840 AC: 122740 AN: 1461824 Hom.: 6897 Cov.: 32 AF XY: 0.0858 AC XY: 62430 AN XY: 727224

Gnomad4 AFR exome AF: 0.0124

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.316

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.0535

Gnomad4 NFE exome AF: 0.0715

Gnomad4 OTH exome AF: 0.0914

GnomAD4 genome AF: 0.0702 AC: 10686 AN: 152158 Hom.: 575 Cov.: 31 AF XY: 0.0744 AC XY: 5538 AN XY: 74388

Gnomad4 AFR AF: 0.0147

Gnomad4 AMR AF: 0.0975

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.0513

Gnomad4 NFE AF: 0.0747

Gnomad4 OTH AF: 0.0749

Alfa AF: 0.0787 Hom.: 1358

Bravo AF: 0.0711

TwinsUK AF: 0.0707 AC: 262

ALSPAC AF: 0.0734 AC: 283

ESP6500AA AF: 0.0182 AC: 80

ESP6500EA AF: 0.0777 AC: 668

ExAC AF: 0.103 AC: 12462

Asia WGS AF: 0.184 AC: 639 AN: 3478

EpiCase AF: 0.0818

EpiControl AF: 0.0857

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
Cadd	Uncertain	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.020	P;P;P
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.078
Sift	Benign	0.16	T
Sift4G	Benign	0.33	T
Polyphen		0.029	B
Vest4		0.13
MPC		0.0031
ClinPred		0.032	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.042
gMVP		0.71

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: rs1056104; hg19: chr2-39008949; COSMIC: COSV56140213;