rs368527531

Variant names:

• chr3-40532043-G-T
• rs368527531
• NM_198484.5:c.273G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-40532043-G-T
• chr3-40532043-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_198484.5(ZNF621):​c.273G>T​(p.Trp91Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,459,180 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. W91R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: ZNF621 NM_198484.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00500
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.067745835).

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.273G>T	p.Trp91Cys	missense	Exon 5 of 5	NP_940886.1	Q6ZSS3-1
	ZNF621	NM_001098414.3		c.273G>T	p.Trp91Cys	missense	Exon 5 of 5	NP_001091884.1	Q6ZSS3-1
	ZNF621	NM_001287245.2		c.273G>T	p.Trp91Cys	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.273G>T	p.Trp91Cys	missense	Exon 5 of 5	ENSP00000340841.5	Q6ZSS3-1
	ZNF621	ENST00000403205.6	TSL:1	c.273G>T	p.Trp91Cys	missense	Exon 5 of 5	ENSP00000386051.2	Q6ZSS3-1
	ZNF621	ENST00000431278.5	TSL:1	c.-61G>T		5_prime_UTR	Exon 4 of 4	ENSP00000413236.1	C9JZC2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000402 AC: 10 AN: 248916 AF XY: 0.0000519

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1459180 Hom.: 0 Cov.: 31 AF XY: 0.0000207 AC XY: 15 AN XY: 725770

African (AFR) AF: 0.00 AC: 0 AN: 33388

American (AMR) AF: 0.00 AC: 0 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.000290 AC: 25 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110974

Other (OTH) AF: 0.00 AC: 0 AN: 60304

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000659 AC: 8

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	0.30
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.063	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.0050
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.037
Sift	Benign	0.17	T
Sift4G	Benign	0.20	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.49		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.17
MPC		0.28
ClinPred		0.057	T
GERP RS		-0.87
Varity_R		0.093
gMVP		0.28
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs368527531; hg19: chr3-40573534;