10-45626349-T-A

Variant names:

• chr10-45626349-T-A
• rs202064320
• NM_174890.4:c.1474A>T

Variant summary

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

The NM_174890.4(ZFAND4):​c.1474A>T​(p.Arg492*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: ZFAND4 NM_174890.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 0 publications found

Genes affected

ZFAND4 (HGNC:23504): (zinc finger AN1-type containing 4) Predicted to enable zinc ion binding activity. [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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFAND4	NM_174890.4	c.1474A>T	p.Arg492*	stop_gained	Exon 7 of 10	ENST00000344646.10	NP_777550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFAND4	ENST00000344646.10	c.1474A>T	p.Arg492*	stop_gained	Exon 7 of 10	1	NM_174890.4	ENSP00000339484.5
ZFAND4	ENST00000374366.7	c.1252A>T	p.Arg418*	stop_gained	Exon 8 of 11	1		ENSP00000363486.3
ZFAND4	ENST00000374370.1	n.1194A>T		non_coding_transcript_exon_variant	Exon 4 of 7	2
ZFAND4	ENST00000374371.6	c.570-8089A>T		intron_variant	Intron 5 of 6	5		ENSP00000363491.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.54
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.82	D
PhyloP100		1.5
Vest4		0.13
GERP RS		1.8
Mutation Taster		=13/187	disease causing (fs/PTC)

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: rs202064320; hg19: chr10-46121797;