chr2-38781872-C-G

Variant names:

• chr2-38781872-C-G
• NM_024775.10:c.484C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024775.10(GEMIN6):​c.484C>G​(p.His162Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GEMIN6 NM_024775.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.35
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22149023).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024775.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GEMIN6	NM_024775.10	MANE Select	c.484C>G	p.His162Asp	missense	Exon 3 of 3	NP_079051.9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GEMIN6	ENST00000281950.8	TSL:1 MANE Select	c.484C>G	p.His162Asp	missense	Exon 3 of 3	ENSP00000281950.2	Q8WXD5
	GEMIN6	ENST00000409011.5	TSL:1	c.*342C>G		3_prime_UTR	Exon 6 of 6	ENSP00000387191.1	B9A037
	GEMIN6	ENST00000911088.1		c.484C>G	p.His162Asp	missense	Exon 3 of 3	ENSP00000581147.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.12
Sift	Benign	0.032	D
Sift4G	Benign	0.18	T
Polyphen		0.46	P
Vest4		0.20
MutPred		0.69		Gain of loop (P = 0.0166)
MVP		0.68
MPC		0.0021
ClinPred		0.79	D
GERP RS		5.8
Varity_R		0.19
gMVP		0.69
Mutation Taster		=89/11	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

hg19: chr2-39009014;