chr10-45626111-G-T

Position:

• chr10-45626111-G-T

Variant summary

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

The NM_174890.4(ZFAND4):​c.1712C>A​(p.Ala571Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFAND4 NM_174890.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01

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

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
ZFAND4	NM_174890.4	c.1712C>A	p.Ala571Asp	missense_variant	7/10	ENST00000344646.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFAND4	ENST00000344646.10	c.1712C>A	p.Ala571Asp	missense_variant	7/10	1	NM_174890.4	P1
ZFAND4	ENST00000374366.7	c.1490C>A	p.Ala497Asp	missense_variant	8/11	1
ZFAND4	ENST00000374371.6	c.570-7851C>A		intron_variant		5
ZFAND4	ENST00000374370.1	n.1432C>A		non_coding_transcript_exon_variant	4/7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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 16, 2021

The c.1712C>A (p.A571D) alteration is located in exon 7 (coding exon 6) of the ZFAND4 gene. This alteration results from a C to A substitution at nucleotide position 1712, causing the alanine (A) at amino acid position 571 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	Benign	0.26
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D;D
Sift4G	Benign	0.12	T;T
Polyphen		0.96	.;D
Vest4		0.66
MutPred		0.49		.;Loss of MoRF binding (P = 0.0446);
MVP		0.56
MPC		0.22
ClinPred		0.94	D
GERP RS		5.7
Varity_R		0.36
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: chr10-46121559;