19-37635092-T-G

Position:

• chr19-37635092-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001320669.3(ZFP30):​c.1449A>C​(p.Gln483His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFP30 NM_001320669.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.70

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2434285).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP30	NM_001320669.3	c.1449A>C	p.Gln483His	missense_variant	6/6	ENST00000684514.1	NP_001307598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP30	ENST00000684514.1	c.1449A>C	p.Gln483His	missense_variant	6/6		NM_001320669.3	ENSP00000508019.1
ZFP30	ENST00000351218.6	c.1449A>C	p.Gln483His	missense_variant	6/6	1		ENSP00000343581.1
ZFP30	ENST00000514101.6	c.1449A>C	p.Gln483His	missense_variant	6/6	1		ENSP00000422930.2
ZFP30	ENST00000589018.5	c.232+8173A>C		intron_variant		5		ENSP00000467387.1

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

Mar 01, 2024

The c.1449A>C (p.Q483H) alteration is located in exon 6 (coding exon 4) of the ZFP30 gene. This alteration results from a A to C substitution at nucleotide position 1449, causing the glutamine (Q) at amino acid position 483 to be replaced by a histidine (H). 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	Pathogenic	0.83
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.015	.;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.82	L;L
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.5	N;N
REVEL	Benign	0.091
Sift	Benign	0.13	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.97	D;D
Vest4		0.16
MutPred		0.42		Loss of MoRF binding (P = 0.0918);Loss of MoRF binding (P = 0.0918);
MVP		0.32
MPC		0.48
ClinPred		0.86	D
GERP RS		-2.2
Varity_R		0.090
gMVP		0.12

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: chr19-38125993;