2-110577006-C-A

Variant names:

• chr2-110577006-C-A
• rs761147198
• NM_001123363.4:c.19G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001123363.4(RGPD6):​c.19G>T​(p.Asp7Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 5)
  • Exomes 𝑓: 0.000051 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD6 NM_001123363.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.03
• Publications: 0 publications found

Genes affected

RGPD6 (HGNC:32419): (RANBP2 like and GRIP domain containing 6) 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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017768085).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001123363.4. 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
	RGPD6	NM_001123363.4	MANE Select	c.19G>T	p.Asp7Tyr	missense	Exon 1 of 23	NP_001116835.1
	RGPD6	NM_001386145.1		c.19G>T	p.Asp7Tyr	missense	Exon 1 of 23	NP_001373074.1
	RGPD6	NM_001037866.2		c.19G>T	p.Asp7Tyr	missense	Exon 1 of 19	NP_001032955.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGPD6	ENST00000329516.8	TSL:1 MANE Select	c.19G>T	p.Asp7Tyr	missense	Exon 1 of 23	ENSP00000330842.3	Q99666-1
	RGPD6	ENST00000696446.1		c.19G>T	p.Asp7Tyr	missense	Exon 1 of 24	ENSP00000512633.1	A0A8Q3SIN4
	RGPD6	ENST00000918437.1		c.19G>T	p.Asp7Tyr	missense	Exon 1 of 22	ENSP00000588496.1

Frequencies

GnomAD3 genomes AF: 0.000120 AC: 3 AN: 25012 Hom.: 0 Cov.: 5

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00450

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

GnomAD2 exomes AF: 0.0000610 AC: 1 AN: 16388 AF XY: 0.000105

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00112

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000511 AC: 31 AN: 606898 Hom.: 0 Cov.: 9 AF XY: 0.0000711 AC XY: 21 AN XY: 295340

African (AFR) AF: 0.00 AC: 0 AN: 9208

American (AMR) AF: 0.00 AC: 0 AN: 11262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8424

East Asian (EAS) AF: 0.00475 AC: 31 AN: 6528

South Asian (SAS) AF: 0.00 AC: 0 AN: 28246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1458

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 507590

Other (OTH) AF: 0.00 AC: 0 AN: 20372

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000120 AC: 3 AN: 25012 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 12770

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 5368

American (AMR) AF: 0.00 AC: 0 AN: 3542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 808

East Asian (EAS) AF: 0.00450 AC: 3 AN: 666

South Asian (SAS) AF: 0.00 AC: 0 AN: 376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 58

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12512

Other (OTH) AF: 0.00 AC: 0 AN: 350

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000716 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.62
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.63	T
PhyloP100		3.0
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.15
Sift	Benign	0.11	T
Sift4G	Uncertain	0.0020	D
Vest4		0.26
MutPred		0.23		Loss of disorder (P = 0.0424)
MVP		0.29
MPC		1.9
ClinPred		0.19	T
GERP RS		1.0
PromoterAI		0.058	Neutral
gMVP		0.10
Mutation Taster		=99/1	polymorphism

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: rs761147198; hg19: chr2-111334583;