NM_001214909.2:c.286C>G

Variant names:

• chr16-30397536-C-G
• rs200032704
• NM_001214909.2:c.286C>G

Variant summary

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

The NM_001214909.2(ZNF48):​c.286C>G​(p.Arg96Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. R96Q) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ZNF48 NM_001214909.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.701
• Publications: 0 publications found

Genes affected

ZNF48 (HGNC:13114): (zinc finger protein 48) Enables identical protein binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.10196814).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001214909.2. 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
	ZNF48	NM_001214909.2	MANE Select	c.286C>G	p.Arg96Gly	missense	Exon 3 of 3	NP_001201838.1	Q96MX3
	ZNF48	NM_001214906.1		c.286C>G	p.Arg96Gly	missense	Exon 3 of 3	NP_001201835.1	Q96MX3
	ZNF48	NM_152652.3		c.286C>G	p.Arg96Gly	missense	Exon 2 of 2	NP_689865.2	Q96MX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF48	ENST00000613509.2	TSL:2 MANE Select	c.286C>G	p.Arg96Gly	missense	Exon 3 of 3	ENSP00000480262.1	Q96MX3
	ZNF48	ENST00000320159.2	TSL:1	c.286C>G	p.Arg96Gly	missense	Exon 2 of 2	ENSP00000324056.2	Q96MX3
	ZNF48	ENST00000872220.1		c.286C>G	p.Arg96Gly	missense	Exon 3 of 3	ENSP00000542279.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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 Cov.: 85

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152160 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74326

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.70
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.067
Sift	Uncertain	0.017	D
Sift4G	Benign	0.30	T
Polyphen		0.18	B
Vest4		0.19
MutPred		0.31		Loss of solvent accessibility (P = 0.0159)
MVP		0.31
MPC		0.51
ClinPred		0.26	T
GERP RS		3.6
Varity_R		0.11
gMVP		0.43

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

Other links and lift over

dbSNP: rs200032704; hg19: chr16-30408857;