19-37635341-A-C

Position:

• chr19-37635341-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001320669.3(ZFP30):​c.1200T>G​(p.His400Gln) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFP30 NM_001320669.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.392

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.919

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP30	NM_001320669.3	c.1200T>G	p.His400Gln	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.1200T>G	p.His400Gln	missense_variant	6/6		NM_001320669.3	ENSP00000508019.1
ZFP30	ENST00000351218.6	c.1200T>G	p.His400Gln	missense_variant	6/6	1		ENSP00000343581.1
ZFP30	ENST00000514101.6	c.1200T>G	p.His400Gln	missense_variant	6/6	1		ENSP00000422930.2
ZFP30	ENST00000589018.5	c.232+7924T>G		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

Oct 03, 2024

The c.1200T>G (p.H400Q) alteration is located in exon 6 (coding exon 4) of the ZFP30 gene. This alteration results from a T to G substitution at nucleotide position 1200, causing the histidine (H) at amino acid position 400 to be replaced by a glutamine (Q). 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	0.98
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T;T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.030
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.55	.;T
M_CAP	Benign	0.083	D
MetaRNN	Pathogenic	0.92	D;D
MetaSVM	Uncertain	0.65	D
MutationAssessor	Pathogenic	3.2	M;M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-7.9	D;D
REVEL	Pathogenic	0.66
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.74
MutPred		0.75		Gain of disorder (P = 0.101);Gain of disorder (P = 0.101);
MVP		0.92
MPC		0.50
ClinPred		1.0	D
GERP RS		1.7
Varity_R		0.77
gMVP		0.26

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: chr19-38126242;