rs3777218

Variant names:

• chr5-95777162-T-A
• rs3777218
• NM_014899.4:c.1283-3090T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-95777162-T-A
• chr5-95777162-T-C

Variant summary

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

The NM_014899.4(RHOBTB3):​c.1283-3090T>A variant causes a intron 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: 32)
• Consequence: RHOBTB3 NM_014899.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 7 publications found

Genes affected

RHOBTB3 (HGNC:18757): (Rho related BTB domain containing 3) Enables ATP binding activity and small GTPase binding activity. Involved in retrograde transport, endosome to Golgi. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

GLRX (HGNC:4330): (glutaredoxin) This gene encodes a member of the glutaredoxin family. The encoded protein is a cytoplasmic enzyme catalyzing the reversible reduction of glutathione-protein mixed disulfides. This enzyme highly contributes to the antioxidant defense system. It is crucial for several signalling pathways by controlling the S-glutathionylation status of signalling mediators. It is involved in beta-amyloid toxicity and Alzheimer's disease. Multiple alternatively spliced transcript variants encoding the same protein have been identified. [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=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOBTB3	NM_014899.4	c.1283-3090T>A		intron_variant	Intron 8 of 11	ENST00000379982.8	NP_055714.3
RHOBTB3	XM_011543279.3	c.917-3090T>A		intron_variant	Intron 7 of 10		XP_011541581.1
RHOBTB3	XM_017009237.2	c.701-3090T>A		intron_variant	Intron 8 of 11		XP_016864726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOBTB3	ENST00000379982.8	c.1283-3090T>A		intron_variant	Intron 8 of 11	1	NM_014899.4	ENSP00000369318.3
RHOBTB3	ENST00000504179.5	c.176-3090T>A		intron_variant	Intron 2 of 5	5		ENSP00000422360.1
RHOBTB3	ENST00000510313.1	c.26-3090T>A		intron_variant	Intron 1 of 3	2		ENSP00000424844.1
GLRX	ENST00000508780.5	c.*7-25702A>T		intron_variant	Intron 2 of 2	4		ENSP00000422708.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.53
PhyloP100		-0.23

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: rs3777218; hg19: chr5-95112866;