chr6-89365640-A-G

Variant names:

• chr6-89365640-A-G
• rs1062108
• NM_021244.5:c.*2416T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021244.5(RRAGD):​c.*2416T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 152,106 control chromosomes in the GnomAD database, including 36,480 homozygotes. 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: 𝑓 0.68 (36480 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: RRAGD NM_021244.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 10 publications found

Genes affected

RRAGD (HGNC:19903): (Ras related GTP binding D) RRAGD is a monomeric guanine nucleotide-binding protein, or G protein. By binding GTP or GDP, small G proteins act as molecular switches in numerous cell processes and signaling pathways.[supplied by OMIM, Apr 2004]

RRAGD Gene-Disease associations (from GenCC):

• hypomagnesemia 7, renal, with or without dilated cardiomyopathy

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021244.5. 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
	RRAGD	NM_021244.5	MANE Select	c.*2416T>C		3_prime_UTR	Exon 7 of 7	NP_067067.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRAGD	ENST00000369415.9	TSL:1 MANE Select	c.*2416T>C		3_prime_UTR	Exon 7 of 7	ENSP00000358423.4
	RRAGD	ENST00000359203.3	TSL:2	c.*2416T>C		3_prime_UTR	Exon 6 of 6	ENSP00000352131.2

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103288 AN: 151988 Hom.: 36416 Cov.: 32

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.628

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.680 AC: 103408 AN: 152106 Hom.: 36480 Cov.: 32 AF XY: 0.677 AC XY: 50324 AN XY: 74354

African (AFR) AF: 0.883 AC: 36654 AN: 41516

American (AMR) AF: 0.570 AC: 8711 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2057 AN: 3470

East Asian (EAS) AF: 0.678 AC: 3502 AN: 5168

South Asian (SAS) AF: 0.670 AC: 3229 AN: 4822

European-Finnish (FIN) AF: 0.601 AC: 6347 AN: 10564

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40726 AN: 67976

Other (OTH) AF: 0.633 AC: 1336 AN: 2112

Alfa AF: 0.622 Hom.: 128445

Bravo AF: 0.682

Asia WGS AF: 0.689 AC: 2396 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.4
DANN	Benign	0.53
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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: rs1062108; hg19: chr6-90075359;