NM_198484.5:c.61A>C

Variant names:

• chr3-40529355-A-C
• rs1184262644
• NM_198484.5:c.61A>C

Variant summary

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

The NM_198484.5(ZNF621):​c.61A>C​(p.Thr21Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. T21A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF621 NM_198484.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.970
• Publications: 19 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.61A>C	p.Thr21Pro	missense	Exon 3 of 5	NP_940886.1	Q6ZSS3-1
	ZNF621	NM_001098414.3		c.61A>C	p.Thr21Pro	missense	Exon 3 of 5	NP_001091884.1	Q6ZSS3-1
	ZNF621	NM_001287245.2		c.61A>C	p.Thr21Pro	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.61A>C	p.Thr21Pro	missense	Exon 3 of 5	ENSP00000340841.5	Q6ZSS3-1
	ZNF621	ENST00000403205.6	TSL:1	c.61A>C	p.Thr21Pro	missense	Exon 3 of 5	ENSP00000386051.2	Q6ZSS3-1
	ZNF621	ENST00000431278.5	TSL:1	c.-182-854A>C		intron	N/A	ENSP00000413236.1	C9JZC2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0084	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.97
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.25
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.76		Loss of sheet (P = 0.1158)
MVP		0.52
MPC		0.84
ClinPred		0.98	D
GERP RS		3.6
Varity_R		0.68
gMVP		0.47
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.40		Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1184262644; hg19: chr3-40570846;