2-38781838-T-G

Position:

• chr2-38781838-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000281950.8(GEMIN6):​c.450T>G​(p.Ile150Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GEMIN6 ENST00000281950.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.887

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GEMIN6	NM_024775.10	c.450T>G	p.Ile150Met	missense_variant	3/3	ENST00000281950.8	NP_079051.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GEMIN6	ENST00000281950.8	c.450T>G	p.Ile150Met	missense_variant	3/3	1	NM_024775.10	ENSP00000281950	P1
GEMIN6	ENST00000409011.5	c.*308T>G		3_prime_UTR_variant	6/6	1		ENSP00000387191
GEMIN6	ENST00000409566.1	c.*298T>G		3_prime_UTR_variant	4/4	2		ENSP00000386613

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251046 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135646

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2023

The c.450T>G (p.I150M) alteration is located in exon 3 (coding exon 2) of the GEMIN6 gene. This alteration results from a T to G substitution at nucleotide position 450, causing the isoleucine (I) at amino acid position 150 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.090
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.12	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	0.72	D;D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.50
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.65		Gain of disorder (P = 0.0696);
MVP		0.72
MPC		0.0048
ClinPred		0.68	D
GERP RS		-6.0
Varity_R		0.50
gMVP		0.62

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: rs772887059; hg19: chr2-39008980;