Genetic Variant NM_012265.3:c.1020G>A (chr22-29260201-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_012265.3(RHBDD3):c.1020G>A(p.Glu340Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 6.9e-7 ( 0 hom. )

Consequence

RHBDD3
NM_012265.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0860

Publications

1 publications found

Variant links:

Genes affected

RHBDD3 (HGNC:1308): (rhomboid domain containing 3) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within several processes, including liver development; negative regulation of natural killer cell activation; and positive regulation of protein catabolic process. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

RHBDD3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP7

Synonymous conserved (PhyloP=0.086 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHBDD3	NM_012265.3 link	c.1020G>A	p.Glu340Glu	synonymous_variant	Exon 7 of 7	ENST00000216085.12	NP_036397.1	Q9Y3P4A0A024R1J2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RHBDD3	ENST00000216085.12 link	c.1020G>A	p.Glu340Glu	synonymous_variant	Exon 7 of 7	1	NM_012265.3	ENSP00000216085.7	Q9Y3P4
RHBDD3	ENST00000413137.6 link	n.*596G>A		non_coding_transcript_exon_variant	Exon 7 of 7	5		ENSP00000399550.2	F8WFA9
RHBDD3	ENST00000413137.6 link	n.*596G>A		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000399550.2	F8WFA9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1444402

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716970

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33272

American (AMR)

AF:

0.00

AC:

AN:

41756

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25698

East Asian (EAS)

AF:

0.0000256

AC:

AN:

38996

South Asian (SAS)

AF:

0.00

AC:

AN:

83534

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51464

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1104214

Other (OTH)

AF:

0.00

AC:

AN:

59718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

5.0

(source)

DANN

Benign

0.89

PhyloP100

0.086

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over