4-141233766-C-T

Variant names:

• chr4-141233766-C-T
• rs770158192
• NM_014487.6:c.740C>T

Variant summary

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

The NM_014487.6(ZNF330):​c.740C>T​(p.Ala247Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,400 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. A247G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF330 NM_014487.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.30
• Publications: 0 publications found

Genes affected

ZNF330 (HGNC:15462): (zinc finger protein 330) Predicted to enable zinc ion binding activity. Located in chromosome, centromeric region; midbody; and nucleolus. [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=0.18257871).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014487.6. 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
	ZNF330	NM_014487.6	MANE Select	c.740C>T	p.Ala247Val	missense	Exon 10 of 10	NP_055302.1	Q9Y3S2
	ZNF330	NM_001292002.2		c.560C>T	p.Ala187Val	missense	Exon 9 of 9	NP_001278931.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF330	ENST00000262990.9	TSL:1 MANE Select	c.740C>T	p.Ala247Val	missense	Exon 10 of 10	ENSP00000262990.4	Q9Y3S2
	ZNF330	ENST00000955956.1		c.740C>T	p.Ala247Val	missense	Exon 10 of 10	ENSP00000626015.1
	ZNF330	ENST00000955957.1		c.740C>T	p.Ala247Val	missense	Exon 10 of 10	ENSP00000626016.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461400 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726996

African (AFR) AF: 0.00 AC: 0 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111726

Other (OTH) AF: 0.0000166 AC: 1 AN: 60366

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0037	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.3
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.11
Sift	Benign	0.031	D
Sift4G	Benign	0.27	T
Polyphen		0.19	B
Vest4		0.32
MutPred		0.61		Gain of sheet (P = 0.0507)
MVP		0.082
MPC		0.20
ClinPred		0.73	D
GERP RS		5.3
Varity_R		0.19
gMVP		0.23
Mutation Taster		=57/43	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: rs770158192; hg19: chr4-142154920;