2-107871445-A-T

Variant names:

• chr2-107871445-A-T
• rs832358
• NM_182588.3:c.3441A>T

Variant summary

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

The NM_182588.3(RGPD4):​c.3441A>T​(p.Leu1147Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000706 in 991,166 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/20 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: 𝑓 0.0 (0 hom., cov: 4)
  • Exomes 𝑓: 0.0000071 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD4 NM_182588.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

Genes affected

RGPD4 (HGNC:32417): (RANBP2 like and GRIP domain containing 4) Predicted to contribute to GTPase activator activity. Predicted to be involved in NLS-bearing protein import into nucleus. Predicted to be part of nuclear pore. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LOC124906057 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGPD4	NM_182588.3	c.3441A>T	p.Leu1147Phe	missense_variant	Exon 20 of 23	ENST00000408999.4	NP_872394.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGPD4	ENST00000408999.4	c.3441A>T	p.Leu1147Phe	missense_variant	Exon 20 of 23	1	NM_182588.3	ENSP00000386810.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 38614 Hom.: 0 Cov.: 4 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000706 AC: 7 AN: 991166 Hom.: 0 Cov.: 30 AF XY: 0.00000806 AC XY: 4 AN XY: 496284

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000947

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 38614 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 18940

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.41	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.67	N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.19
Sift	Benign	0.54	T
Sift4G	Uncertain	0.055	T
Polyphen		0.71	P
Vest4		0.74
MutPred		0.65		Loss of sheet (P = 0.0126);
MVP		0.099
ClinPred		0.47	T
GERP RS		2.3
Varity_R		0.11
gMVP		0.027

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

Publications

LitVar

Other links and lift over

dbSNP: rs832358; hg19: chr2-108487901;