rs765657757

Variant names:

• chr2-38781851-G-A
• NM_024775.10:c.463G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-38781851-G-A
• chr2-38781851-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024775.10(GEMIN6):​c.463G>A​(p.Val155Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,182 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V155F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GEMIN6 NM_024775.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08143997).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GEMIN6	NM_024775.10	c.463G>A	p.Val155Ile	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.463G>A	p.Val155Ile	missense_variant	Exon 3 of 3	1	NM_024775.10	ENSP00000281950.2
GEMIN6	ENST00000409011.5	c.*321G>A		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000387191.1
GEMIN6	ENST00000409566.1	c.*311G>A		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000386613.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460182 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726062

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.72
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.039
Sift	Benign	0.90	T
Sift4G	Benign	0.94	T
Polyphen		0.016	B
Vest4		0.17
MutPred		0.52		Gain of helix (P = 0.1736);
MVP		0.28
MPC		0.0024
ClinPred		0.29	T
GERP RS		4.0
Varity_R		0.016
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-39008993;