14-39136338-T-A

Variant names:

• chr14-39136338-T-A
• rs9322993
• NM_003616.3:c.771-102T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003616.3(GEMIN2):​c.771-102T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000189 in 530,130 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: GEMIN2 NM_003616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494
• Publications: 5 publications found

Genes affected

GEMIN2 (HGNC:10884): (gem nuclear organelle associated protein 2) This gene encodes one of the proteins found in the SMN complex, which consists of several gemin proteins and the protein known as the survival of motor neuron protein. The SMN complex is localized to a subnuclear compartment called gems (gemini of coiled bodies) and is required for assembly of spliceosomal snRNPs and for pre-mRNA splicing. This protein interacts directly with the survival of motor neuron protein and it is required for formation of the SMN complex. A knockout mouse targeting the mouse homolog of this gene exhibited disrupted snRNP assembly and motor neuron degeneration. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003616.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GEMIN2	NM_003616.3	MANE Select	c.771-102T>A		intron	N/A	NP_003607.2
	GEMIN2	NM_001009182.2		c.726-102T>A		intron	N/A	NP_001009182.2
	GEMIN2	NM_001009183.2		c.712-102T>A		intron	N/A	NP_001009183.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GEMIN2	ENST00000308317.12	TSL:1 MANE Select	c.771-102T>A		intron	N/A	ENSP00000308533.7
	GEMIN2	ENST00000250379.13	TSL:1	c.726-102T>A		intron	N/A	ENSP00000250379.9
	GEMIN2	ENST00000396249.7	TSL:1	c.712-102T>A		intron	N/A	ENSP00000379548.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000189 AC: 1 AN: 530130 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 287880

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 13558

American (AMR) AF: 0.00 AC: 0 AN: 26238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17888

East Asian (EAS) AF: 0.00 AC: 0 AN: 31792

South Asian (SAS) AF: 0.00 AC: 0 AN: 53986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3730

European-Non Finnish (NFE) AF: 0.00000322 AC: 1 AN: 310840

Other (OTH) AF: 0.00 AC: 0 AN: 28922

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.0
DANN	Benign	0.78
PhyloP100		-0.49

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: rs9322993; hg19: chr14-39605542;