3-40532119-C-T

Variant names:

• chr3-40532119-C-T
• NM_198484.5:c.349C>T

Variant summary

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

The NM_198484.5(ZNF621):​c.349C>T​(p.Leu117Phe) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF621 NM_198484.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.436
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07496098).

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.349C>T	p.Leu117Phe	missense	Exon 5 of 5	NP_940886.1	Q6ZSS3-1
	ZNF621	NM_001098414.3		c.349C>T	p.Leu117Phe	missense	Exon 5 of 5	NP_001091884.1	Q6ZSS3-1
	ZNF621	NM_001287245.2		c.349C>T	p.Leu117Phe	missense	Exon 5 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.349C>T	p.Leu117Phe	missense	Exon 5 of 5	ENSP00000340841.5	Q6ZSS3-1
	ZNF621	ENST00000403205.6	TSL:1	c.349C>T	p.Leu117Phe	missense	Exon 5 of 5	ENSP00000386051.2	Q6ZSS3-1
	ZNF621	ENST00000431278.5	TSL:1	c.16C>T	p.Leu6Phe	missense	Exon 4 of 4	ENSP00000413236.1	C9JZC2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Benign	0.094
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.7
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.44
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.065
Sift	Benign	0.39	T
Sift4G	Benign	0.34	T
Polyphen		0.0030	B
Vest4		0.038
MutPred		0.30		Loss of loop (P = 0.1242)
MVP		0.18
MPC		0.32
ClinPred		0.10	T
GERP RS		1.2
Varity_R		0.031
gMVP		0.052
Mutation Taster		=100/0	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

hg19: chr3-40573610;