NM_138802.3:c.610C>G

Variant names:

• chr2-219208593-C-G
• rs745481290
• NM_138802.3:c.610C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138802.3(ZFAND2B):​c.610C>G​(p.Arg204Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. R204W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFAND2B NM_138802.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.51
• Publications: 0 publications found

Genes affected

ZFAND2B (HGNC:25206): (zinc finger AN1-type containing 2B) This gene encodes a protein containing AN1-type zinc-fingers and ubiquitin-interacting motifs. The encoded protein likely associates with the proteosome to stimulate the degradation of toxic or misfolded proteins. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24769148).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138802.3. 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
	ZFAND2B	NM_138802.3	MANE Select	c.610C>G	p.Arg204Gly	missense	Exon 7 of 9	NP_620157.1	Q8WV99-1
	ZFAND2B	NM_001437630.1		c.610C>G	p.Arg204Gly	missense	Exon 8 of 9	NP_001424559.1
	ZFAND2B	NM_001437631.1		c.610C>G	p.Arg204Gly	missense	Exon 8 of 9	NP_001424560.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFAND2B	ENST00000289528.10	TSL:1 MANE Select	c.610C>G	p.Arg204Gly	missense	Exon 7 of 9	ENSP00000289528.5	Q8WV99-1
	ZFAND2B	ENST00000409336.5	TSL:5	c.610C>G	p.Arg204Gly	missense	Exon 8 of 10	ENSP00000386898.1	Q8WV99-1
	ZFAND2B	ENST00000444522.6	TSL:5	c.610C>G	p.Arg204Gly	missense	Exon 8 of 10	ENSP00000411334.3	Q8WV99-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251284 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.5
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.012	D
Polyphen		0.98	D
Vest4		0.44
MutPred		0.46		Loss of phosphorylation at S209 (P = 0.2101)
MVP		0.49
MPC		0.23
ClinPred		0.97	D
GERP RS		5.4
PromoterAI		-0.0035	Neutral
Varity_R		0.50
gMVP		0.61
Mutation Taster		=34/66	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs745481290; hg19: chr2-220073315;