Genetic Variant DRC4:p.Arg369Leu (chr16-90040394-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000268699.9(GAS8):c.1106G>T(p.Arg369Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,228 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R369C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GAS8
ENST00000268699.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.59

Publications

0 publications found

Variant links:

Genes affected

DRC4 (HGNC:4166): (growth arrest specific 8) This gene includes 11 exons spanning 25 kb and maps to a region of chromosome 16 that is sometimes deleted in breast and prostrate cancer. The second intron contains an apparently intronless gene, C16orf3, that is transcribed in the opposite orientation. This gene is a putative tumor suppressor gene. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

DRC4 links:

URAHP (HGNC:):

URAHP links:

URAHP (HGNC:43695): (urate (hydroxyiso-) hydrolase, pseudogene) Predicted to enable hydroxyisourate hydrolase activity. Predicted to be involved in allantoin metabolic process; purine-containing compound catabolic process; and urate catabolic process. Predicted to be active in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

URAHP links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000268699.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DRC4	NM_001481.3	MANE Select	c.1106G>T	p.Arg369Leu	missense	Exon 9 of 11	NP_001472.1
DRC4	NM_001286209.2		c.1031G>T	p.Arg344Leu	missense	Exon 9 of 11	NP_001273138.1
DRC4	NM_001286205.2		c.857G>T	p.Arg286Leu	missense	Exon 9 of 11	NP_001273134.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GAS8	ENST00000268699.9	TSL:1 MANE Select	c.1106G>T	p.Arg369Leu	missense	Exon 9 of 11	ENSP00000268699.4
URAHP	ENST00000409873.5	TSL:1	n.716C>A		non_coding_transcript_exon	Exon 5 of 5
GAS8	ENST00000566266.5	TSL:1	n.*1066G>T		non_coding_transcript_exon	Exon 8 of 10	ENSP00000454343.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459228

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725640

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33432

American (AMR)

AF:

0.00

AC:

AN:

44480

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39574

South Asian (SAS)

AF:

0.00

AC:

AN:

85672

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5664

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110890

Other (OTH)

AF:

0.00

AC:

AN:

60268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.064

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.065

MetaRNN

Uncertain

0.69

MetaSVM

Benign

-0.67

PhyloP100

5.6

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.28

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.026

Polyphen

0.93

Vest4

0.73

MutPred

0.22

Loss of MoRF binding (P = 0.0432)

MVP

0.65

MPC

0.14

ClinPred

0.97

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

gMVP

0.38

Mutation Taster

=78/22

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over