chr22-45417619-A-G

Position:

• chr22-45417619-A-G

Variant summary

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

The NM_015653.5(RIBC2):​c.229A>G​(p.Asn77Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RIBC2 NM_015653.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.16

Genes affected

RIBC2 (HGNC:13241): (RIB43A domain with coiled-coils 2) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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/exons	MANE	UniProt
RIBC2	NM_015653.5	c.229A>G	p.Asn77Asp	missense_variant	3/7	ENST00000614167.2
RIBC2	XM_005261524.5	c.10A>G	p.Asn4Asp	missense_variant	3/7
RIBC2	XM_017028766.2	c.229A>G	p.Asn77Asp	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIBC2	ENST00000614167.2	c.229A>G	p.Asn77Asp	missense_variant	3/7	1	NM_015653.5	P1
RIBC2	ENST00000621287.1	n.99A>G		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.214A>G (p.N72D) alteration is located in exon 3 (coding exon 3) of the RIBC2 gene. This alteration results from a A to G substitution at nucleotide position 214, causing the asparagine (N) at amino acid position 72 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.87	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.52	T
Sift4G	Benign	0.074	T
Vest4		0.72
MVP		0.56
ClinPred		0.99	D
GERP RS		4.8
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-45813499;