6-38116698-A-G

Position:

• chr6-38116698-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021943.3(ZFAND3):​c.488A>G​(p.Lys163Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZFAND3 NM_021943.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.70

Genes affected

ZFAND3 (HGNC:18019): (zinc finger AN1-type containing 3) Predicted to enable DNA binding activity and zinc ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFAND3	NM_021943.3	c.488A>G	p.Lys163Arg	missense_variant	5/6	ENST00000287218.9
ZFAND3	NM_001410904.1	c.422A>G	p.Lys141Arg	missense_variant	4/5
ZFAND3	XM_017011171.3	c.440A>G	p.Lys147Arg	missense_variant	4/5
ZFAND3	XM_011514790.3	c.361+34241A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFAND3	ENST00000287218.9	c.488A>G	p.Lys163Arg	missense_variant	5/6	1	NM_021943.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461808 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727196

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2023

The c.488A>G (p.K163R) alteration is located in exon 5 (coding exon 5) of the ZFAND3 gene. This alteration results from a A to G substitution at nucleotide position 488, causing the lysine (K) at amino acid position 163 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.75	N;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.33	N;N
REVEL	Uncertain	0.33
Sift	Benign	0.39	T;T
Sift4G	Benign	0.24	T;T
Polyphen		1.0	D;.
Vest4		0.84
MutPred		0.59		Loss of ubiquitination at K163 (P = 0.0134);.;
MVP		0.27
MPC		2.3
ClinPred		0.93	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.63

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-38084474;