Genetic Variant NM_001382344.1:c.33C>T (chr2-86942269-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001382344.1(RGPD1):c.33C>T(p.Tyr11Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000517 in 1,606,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

RGPD1
NM_001382344.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0730

Publications

1 publications found

Variant links:

Genes affected

RGPD1 (HGNC:32414): (RANBP2 like and GRIP domain containing 1) 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]

RGPD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 2-86942269-C-T is Benign according to our data. Variant chr2-86942269-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2651104.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.073 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382344.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGPD1	NM_001382344.1	MANE Select	c.33C>T	p.Tyr11Tyr	synonymous	Exon 1 of 23	NP_001369273.1	A0A286YES2
RGPD1	NM_001410915.1		c.73-9027C>T		intron	N/A	NP_001397844.1	F8VYC4
RGPD1	NM_001024457.4		c.49-9027C>T		intron	N/A	NP_001019628.3	P0DJD0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGPD1	ENST00000641458.2	MANE Select	c.33C>T	p.Tyr11Tyr	synonymous	Exon 1 of 23	ENSP00000492954.1	A0A286YES2
RGPD1	ENST00000398193.8	TSL:1	c.73-9027C>T		intron	N/A	ENSP00000381253.3	F8VYC4
RGPD1	ENST00000641339.1		n.*216-9027C>T		intron	N/A	ENSP00000492933.1	A0A286YEQ5

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

151784

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000433

AC:

AN:

1455002

Hom.:

Cov.:

AF XY:

0.0000415

AC XY:

AN XY:

723502

show subpopulations

African (AFR)

AF:

0.0000602

AC:

AN:

33234

American (AMR)

AF:

0.0000902

AC:

AN:

44344

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25952

East Asian (EAS)

AF:

0.000101

AC:

AN:

39554

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52850

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4128

European-Non Finnish (NFE)

AF:

0.0000387

AC:

AN:

1109702

Other (OTH)

AF:

0.000150

AC:

AN:

60006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.406

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000132

AC:

AN:

151904

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.00118

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000195

AC:

AN:

5130

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10522

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67922

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000219

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

-0.073

PromoterAI

0.0095

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over