2-38781807-G-A

Variant names:

• chr2-38781807-G-A
• rs1056104
• NM_024775.10:c.419G>A

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GEMIN6	NM_024775.10	c.419G>A	p.Gly140Asp	missense_variant	Exon 3 of 3	ENST00000281950.8	NP_079051.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GEMIN6	ENST00000281950.8	c.419G>A	p.Gly140Asp	missense_variant	Exon 3 of 3	1	NM_024775.10	ENSP00000281950.2
GEMIN6	ENST00000409011.5	c.*277G>A		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000387191.1
GEMIN6	ENST00000409566.1	c.*267G>A		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000386613.1

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

GnomAD2 exomes AF: 0.104 AC: 26112 AN: 251324 AF XY: 0.106

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 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

African (AFR) AF: 0.0124 AC: 416 AN: 33480

American (AMR) AF: 0.120 AC: 5345 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2984 AN: 26136

East Asian (EAS) AF: 0.316 AC: 12563 AN: 39698

South Asian (SAS) AF: 0.149 AC: 12871 AN: 86254

European-Finnish (FIN) AF: 0.0535 AC: 2857 AN: 53416

Middle Eastern (MID) AF: 0.109 AC: 630 AN: 5768

European-Non Finnish (NFE) AF: 0.0715 AC: 79554 AN: 1111958

Other (OTH) AF: 0.0914 AC: 5520 AN: 60394

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

African (AFR) AF: 0.0147 AC: 609 AN: 41538

American (AMR) AF: 0.0975 AC: 1487 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3470

East Asian (EAS) AF: 0.289 AC: 1492 AN: 5160

South Asian (SAS) AF: 0.157 AC: 758 AN: 4828

European-Finnish (FIN) AF: 0.0513 AC: 544 AN: 10596

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0747 AC: 5083 AN: 68000

Other (OTH) AF: 0.0749 AC: 158 AN: 2110

Alfa AF: 0.0786 Hom.: 1914

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
PhyloP100		6.0
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
Mutation Taster		=95/5	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: rs1056104; hg19: chr2-39008949; COSMIC: COSV56140213;