19-37635811-A-G

Position:

• chr19-37635811-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Moderate PP5_Moderate

The NM_001320669.3(ZFP30):​c.730T>C​(p.Cys244Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFP30 NM_001320669.3 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 6.80

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.929
• PP5: Variant 19-37635811-A-G is Pathogenic according to our data. Variant chr19-37635811-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 224819.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-37635811-A-G is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP30	NM_001320669.3	c.730T>C	p.Cys244Arg	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.730T>C	p.Cys244Arg	missense_variant	6/6		NM_001320669.3	ENSP00000508019.1
ZFP30	ENST00000351218.6	c.730T>C	p.Cys244Arg	missense_variant	6/6	1		ENSP00000343581.1
ZFP30	ENST00000514101.6	c.730T>C	p.Cys244Arg	missense_variant	6/6	1		ENSP00000422930.2
ZFP30	ENST00000589018.5	c.232+7454T>C		intron_variant		5		ENSP00000467387.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cerebral visual impairment and intellectual disability Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Sep 09, 2015

This study shows that diverse genetic causes underlie CVI. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D;D
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.24	.;T
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.93	D;D
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Pathogenic	4.0	H;H
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-12	D;D
REVEL	Pathogenic	0.74
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.70
MutPred		0.76		Gain of MoRF binding (P = 0.0199);Gain of MoRF binding (P = 0.0199);
MVP		0.96
MPC		0.66
ClinPred		1.0	D
GERP RS		4.0
Varity_R		0.94
gMVP		0.32

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

LitVar

Other links and lift over

dbSNP: rs869312869; hg19: chr19-38126712;