rs1010302141

Variant names:

• chr16-66925016-G-A
• NM_004165.3:c.164C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-66925016-G-A
• chr16-66925016-G-T

Variant summary

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

The NM_004165.3(RRAD):​c.164C>T​(p.Ala55Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000793 in 1,261,464 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: RRAD NM_004165.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10

Genes affected

RRAD (HGNC:10446): (RRAD, Ras related glycolysis inhibitor and calcium channel regulator) Predicted to enable GTP binding activity and calcium channel regulator activity. Predicted to be involved in small GTPase mediated signal transduction. Predicted to be located in cytosol. Predicted to be active in plasma membrane. Implicated in type 2 diabetes mellitus. Biomarker of congestive heart failure. [provided by Alliance of Genome Resources, Apr 2022]

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=0.1323559).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRAD	NM_004165.3	c.164C>T	p.Ala55Val	missense_variant	Exon 2 of 5	ENST00000299759.11	NP_004156.1
RRAD	NM_001128850.2	c.164C>T	p.Ala55Val	missense_variant	Exon 2 of 5		NP_001122322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRAD	ENST00000299759.11	c.164C>T	p.Ala55Val	missense_variant	Exon 2 of 5	1	NM_004165.3	ENSP00000299759.6
RRAD	ENST00000566577.1	c.-65C>T		upstream_gene_variant		5		ENSP00000462559.1
RRAD	ENST00000568915.5	c.-44C>T		upstream_gene_variant		5		ENSP00000461995.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.93e-7 AC: 1 AN: 1261464 Hom.: 0 Cov.: 30 AF XY: 0.00000161 AC XY: 1 AN XY: 619324

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000460

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: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.25	T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.69	T;.
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.55	N;N
REVEL	Benign	0.045
Sift	Benign	0.29	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.0020	B;B
Vest4		0.065
MutPred		0.20		Loss of helix (P = 0.0304);Loss of helix (P = 0.0304);
MVP		0.61
MPC		0.63
ClinPred		0.089	T
GERP RS		3.4
Varity_R		0.066
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-66958919;