chr8-143250417-C-G

Variant names:

• chr8-143250417-C-G
• rs200699856
• NM_173832.6:c.574C>G

Variant summary

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

The NM_173832.6(ZFP41):​c.574C>G​(p.Arg192Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 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. R192C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZFP41 NM_173832.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.151
• Publications: 0 publications found

Genes affected

ZFP41 (HGNC:26786): (ZFP41 zinc finger protein) Enables sequence-specific double-stranded 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]

ENSG00000264668 (HGNC:):

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=0.05220017).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173832.6. 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
	ZFP41	NM_173832.6	MANE Select	c.574C>G	p.Arg192Gly	missense	Exon 2 of 3	NP_776193.3	Q8N8Y5
	ZFP41	NM_001271156.3		c.574C>G	p.Arg192Gly	missense	Exon 2 of 3	NP_001258085.3	Q8N8Y5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP41	ENST00000330701.7	TSL:2 MANE Select	c.574C>G	p.Arg192Gly	missense	Exon 2 of 3	ENSP00000327427.6	Q8N8Y5
	ZFP41	ENST00000520584.6	TSL:1	c.574C>G	p.Arg192Gly	missense	Exon 2 of 3	ENSP00000430465.3	Q8N8Y5
	ENSG00000264668	ENST00000522452.2	TSL:1	c.574C>G	p.Arg192Gly	missense	Exon 2 of 4	ENSP00000428966.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459090 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725468

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110286

Other (OTH) AF: 0.00 AC: 0 AN: 60302

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Uncertain	0.43
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Uncertain	0.98
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.15
PrimateAI	Benign	0.29	T
REVEL	Benign	0.014
Sift4G	Uncertain	0.060	T
Vest4		0.13
MVP		0.14
MPC		0.12
ClinPred		0.21	T
GERP RS		-0.68
Mutation Taster		=91/9	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: rs200699856; hg19: chr8-144332587;