chr6-37819956-C-A

Position:

• chr6-37819956-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021943.3(ZFAND3):​c.11C>A​(p.Ala4Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZFAND3 NM_021943.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.53

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11725509).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFAND3	NM_021943.3	c.11C>A	p.Ala4Asp	missense_variant	1/6	ENST00000287218.9
ZFAND3	NM_001410904.1	c.11C>A	p.Ala4Asp	missense_variant	1/5
ZFAND3	XM_011514790.3	c.11C>A	p.Ala4Asp	missense_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFAND3	ENST00000287218.9	c.11C>A	p.Ala4Asp	missense_variant	1/6	1	NM_021943.3	P1
ZFAND3	ENST00000373391.6	c.11C>A	p.Ala4Asp	missense_variant	1/5	5
ZFAND3	ENST00000474522.5	c.11C>A	p.Ala4Asp	missense_variant	1/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1071464 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 508778

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Aug 17, 2021

The c.11C>A (p.A4D) alteration is located in exon 1 (coding exon 1) of the ZFAND3 gene. This alteration results from a C to A substitution at nucleotide position 11, causing the alanine (A) at amino acid position 4 to be replaced by an aspartic acid (D). 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	Uncertain	0.49
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0094	T;.;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;.
MutationTaster	Benign	0.67	D;D
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.78	N;N;N
REVEL	Benign	0.058
Sift	Uncertain	0.010	D;D;D
Sift4G	Uncertain	0.040	D;D;D
Polyphen		0.18	B;.;.
Vest4		0.31
MutPred		0.16		Loss of catalytic residue at A4 (P = 0.0098);Loss of catalytic residue at A4 (P = 0.0098);Loss of catalytic residue at A4 (P = 0.0098);
MVP		0.043
MPC		0.42
ClinPred		0.85	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.41

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: chr6-37787732;