19-37635492-C-T

Variant names:

• chr19-37635492-C-T
• rs1333603406
• NM_001320669.3:c.1049G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001320669.3(ZFP30):​c.1049G>A​(p.Gly350Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,848 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G350A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZFP30 NM_001320669.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82
• Publications: 0 publications found

Genes affected

ZFP30 (HGNC:29555): (ZFP30 zinc finger protein) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36378914).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320669.3. 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
	ZFP30	NM_001320669.3	MANE Select	c.1049G>A	p.Gly350Asp	missense	Exon 6 of 6	NP_001307598.1	D3Y2A0
	ZFP30	NM_001320666.3		c.1049G>A	p.Gly350Asp	missense	Exon 6 of 6	NP_001307595.1	D3Y2A0
	ZFP30	NM_001320667.3		c.1049G>A	p.Gly350Asp	missense	Exon 6 of 6	NP_001307596.1	Q9Y2G7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP30	ENST00000684514.1	MANE Select	c.1049G>A	p.Gly350Asp	missense	Exon 6 of 6	ENSP00000508019.1	Q9Y2G7
	ZFP30	ENST00000351218.6	TSL:1	c.1049G>A	p.Gly350Asp	missense	Exon 6 of 6	ENSP00000343581.1	Q9Y2G7
	ZFP30	ENST00000514101.6	TSL:1	c.1049G>A	p.Gly350Asp	missense	Exon 6 of 6	ENSP00000422930.2	Q9Y2G7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461848 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.8
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-6.4	D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.40		Gain of solvent accessibility (P = 0.0638)
MVP		0.55
MPC		0.56
ClinPred		0.98	D
GERP RS		4.0
Varity_R		0.74
gMVP		0.053
Mutation Taster		=81/19	polymorphism

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: rs1333603406; hg19: chr19-38126393;