rs1051676191

Variant names:

• chr8-143250043-C-G
• rs1051676191
• NM_173832.6:c.200C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-143250043-C-G
• chr8-143250043-C-T

Variant summary

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

The NM_173832.6(ZFP41):​c.200C>G​(p.Ser67*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZFP41 NM_173832.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• 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: 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_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.200C>G	p.Ser67*	stop_gained	Exon 2 of 3	NP_776193.3	Q8N8Y5
	ZFP41	NM_001271156.3		c.200C>G	p.Ser67*	stop_gained	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.200C>G	p.Ser67*	stop_gained	Exon 2 of 3	ENSP00000327427.6	Q8N8Y5
	ZFP41	ENST00000520584.6	TSL:1	c.200C>G	p.Ser67*	stop_gained	Exon 2 of 3	ENSP00000430465.3	Q8N8Y5
	ENSG00000264668	ENST00000522452.2	TSL:1	c.200C>G	p.Ser67*	stop_gained	Exon 2 of 4	ENSP00000428966.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461856 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.57
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Uncertain	0.22
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.24	N
PhyloP100		1.1
Vest4		0.054
GERP RS		0.92
Mutation Taster		=79/121	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1051676191; hg19: chr8-144332213;