chr3-40532503-C-A

Variant names:

• chr3-40532503-C-A
• rs144763141
• NM_198484.5:c.733C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198484.5(ZNF621):​c.733C>A​(p.Arg245Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R245H) has been classified 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: -1.37
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05103284).

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.733C>A	p.Arg245Ser	missense	Exon 5 of 5	NP_940886.1	Q6ZSS3-1
	ZNF621	NM_001098414.3		c.733C>A	p.Arg245Ser	missense	Exon 5 of 5	NP_001091884.1	Q6ZSS3-1
	ZNF621	NM_001287245.2		c.436+297C>A		intron	N/A	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.733C>A	p.Arg245Ser	missense	Exon 5 of 5	ENSP00000340841.5	Q6ZSS3-1
	ZNF621	ENST00000403205.6	TSL:1	c.733C>A	p.Arg245Ser	missense	Exon 5 of 5	ENSP00000386051.2	Q6ZSS3-1
	ZNF621	ENST00000431278.5	TSL:1	c.400C>A	p.Arg134Ser	missense	Exon 4 of 4	ENSP00000413236.1	C9JZC2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.76
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.47
DANN	Benign	0.23
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.070	N
PhyloP100		-1.4
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.039	B
Vest4		0.19
MutPred		0.50		Loss of MoRF binding (P = 0.0183)
MVP		0.10
MPC		0.21
ClinPred		0.11	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.063
gMVP		0.091
Mutation Taster		=94/6	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: rs144763141; hg19: chr3-40573994;