chr7-1157709-A-C

Position:

• chr7-1157709-A-C

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1 PM2 PP3_Strong

The ENST00000316495.8(ZFAND2A):​c.97T>G​(p.Cys33Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZFAND2A ENST00000316495.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.55

Genes affected

ZFAND2A (HGNC:28073): (zinc finger AN1-type containing 2A) Predicted to enable zinc ion binding activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process and protein targeting to ER. Predicted to act upstream of or within cellular response to arsenic-containing substance and positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Predicted to be located in nucleus. Predicted to be part of proteasome complex. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ZFAND2A (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity ZFN2A_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.959

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFAND2A	NM_182491.4	c.97T>G	p.Cys33Gly	missense_variant	3/5	ENST00000316495.8	NP_872297.2
ZFAND2A	NM_001365383.1	c.97T>G	p.Cys33Gly	missense_variant	3/6		NP_001352312.1
ZFAND2A	NM_001365381.2	c.97T>G	p.Cys33Gly	missense_variant	3/5		NP_001352310.1
ZFAND2A	NR_158186.2	n.375T>G		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFAND2A	ENST00000316495.8	c.97T>G	p.Cys33Gly	missense_variant	3/5	1	NM_182491.4	ENSP00000314619.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

May 03, 2023

The c.97T>G (p.C33G) alteration is located in exon 3 (coding exon 2) of the ZFAND2A gene. This alteration results from a T to G substitution at nucleotide position 97, causing the cysteine (C) at amino acid position 33 to be replaced by a glycine (G). 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	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.55
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Benign	0.41	T;.;D
Eigen	Pathogenic	0.77
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Uncertain	0.29	D
MetaRNN	Pathogenic	0.96	D;D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	4.2	.;.;H
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-12	D;D;D
REVEL	Pathogenic	0.85
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0060	D;.;D
Polyphen		1.0	.;D;D
Vest4		0.98
MutPred		0.75		Loss of stability (P = 0.0047);Loss of stability (P = 0.0047);Loss of stability (P = 0.0047);
MVP		0.98
MPC		0.051
ClinPred		1.0	D
GERP RS		4.1
Varity_R		0.81
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: 0

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: chr7-1197345;