chr3-40529376-C-T

Variant names:

• chr3-40529376-C-T
• NM_198484.5:c.82C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_198484.5(ZNF621):​c.82C>T​(p.Leu28Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF621 NM_198484.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57
• Publications: 0 publications found

Genes affected

ZNF621 (HGNC:24787): (zinc finger protein 621) 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.918

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198484.5. 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
	ZNF621	NM_198484.5	MANE Select	c.82C>T	p.Leu28Phe	missense	Exon 3 of 5	NP_940886.1	Q6ZSS3-1
	ZNF621	NM_001098414.3		c.82C>T	p.Leu28Phe	missense	Exon 3 of 5	NP_001091884.1	Q6ZSS3-1
	ZNF621	NM_001287245.2		c.82C>T	p.Leu28Phe	missense	Exon 3 of 6	NP_001274174.1	Q6ZSS3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF621	ENST00000339296.10	TSL:1 MANE Select	c.82C>T	p.Leu28Phe	missense	Exon 3 of 5	ENSP00000340841.5	Q6ZSS3-1
	ZNF621	ENST00000403205.6	TSL:1	c.82C>T	p.Leu28Phe	missense	Exon 3 of 5	ENSP00000386051.2	Q6ZSS3-1
	ZNF621	ENST00000431278.5	TSL:1	c.-182-833C>T		intron	N/A	ENSP00000413236.1	C9JZC2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.92	D
MetaSVM	Benign	-0.56	T
MutationAssessor	Pathogenic	4.2	H
PhyloP100		1.6
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.85		Gain of helix (P = 0.1736)
MVP		0.50
MPC		0.76
ClinPred		1.0	D
GERP RS		3.5
Varity_R		0.43
gMVP		0.19
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr3-40570867;