19-45090198-T-C

Variant names:

• chr19-45090198-T-C
• rs766609239
• NM_024707.3:c.84T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024707.3(GEMIN7):​c.84T>C​(p.Asp28Asp) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GEMIN7 NM_024707.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• Publications: 1 publications found

Genes affected

GEMIN7 (HGNC:20045): (gem nuclear organelle associated protein 7) The protein encoded by this gene is a component of the core SMN complex, which is required for pre-mRNA splicing in the nucleus. The encoded protein is found in the nucleoplasm, in nuclear "gems" (Gemini of Cajal bodies), and in the cytoplasm. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

MARK4 (HGNC:13538): (microtubule affinity regulating kinase 4) This gene encodes a member of the microtubule affinity-regulating kinase family. These protein kinases phosphorylate microtubule-associated proteins and regulate the transition between stable and dynamic microtubules. The encoded protein is associated with the centrosome throughout mitosis and may be involved in cell cycle control. Expression of this gene is a potential marker for cancer, and the encoded protein may also play a role in Alzheimer's disease. Pseudogenes of this gene are located on both the short and long arm of chromosome 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

GEMIN7-AS1 (HGNC:53773): (GEMIN7 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=-0.299 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024707.3. 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
	GEMIN7	NM_024707.3	MANE Select	c.84T>C	p.Asp28Asp	synonymous	Exon 3 of 3	NP_078983.1	Q9H840
	GEMIN7	NM_001007269.2		c.84T>C	p.Asp28Asp	synonymous	Exon 2 of 2	NP_001007270.1	Q9H840
	GEMIN7	NM_001007270.2		c.84T>C	p.Asp28Asp	synonymous	Exon 3 of 3	NP_001007271.1	Q9H840

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GEMIN7	ENST00000270257.9	TSL:1 MANE Select	c.84T>C	p.Asp28Asp	synonymous	Exon 3 of 3	ENSP00000270257.3	Q9H840
	GEMIN7	ENST00000391951.2	TSL:2	c.84T>C	p.Asp28Asp	synonymous	Exon 2 of 2	ENSP00000375813.1	Q9H840
	GEMIN7	ENST00000591607.1	TSL:3	c.84T>C	p.Asp28Asp	synonymous	Exon 2 of 2	ENSP00000466342.1	Q9H840

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	3.9
DANN	Benign	0.64
PhyloP100		-0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs766609239; hg19: chr19-45593456;