7-1155548-G-A

Variant names:

• chr7-1155548-G-A
• NM_182491.4:c.187C>T

Variant summary

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

The NM_182491.4(ZFAND2A):​c.187C>T​(p.Pro63Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,628 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: 0.0000014 (0 hom.)
• Consequence: ZFAND2A NM_182491.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.66

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]

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 rank	MANE	Protein	UniProt
ZFAND2A	NM_182491.4	c.187C>T	p.Pro63Ser	missense_variant	Exon 4 of 5	ENST00000316495.8	NP_872297.2
ZFAND2A	NM_001365383.1	c.187C>T	p.Pro63Ser	missense_variant	Exon 4 of 6		NP_001352312.1
ZFAND2A	NM_001365381.2	c.187C>T	p.Pro63Ser	missense_variant	Exon 4 of 5		NP_001352310.1
ZFAND2A	NR_158186.2	n.465C>T		non_coding_transcript_exon_variant	Exon 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFAND2A	ENST00000316495.8	c.187C>T	p.Pro63Ser	missense_variant	Exon 4 of 5	1	NM_182491.4	ENSP00000314619.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461628 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727112

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

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

Jan 02, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.187C>T (p.P63S) alteration is located in exon 4 (coding exon 3) of the ZFAND2A gene. This alteration results from a C to T substitution at nucleotide position 187, causing the proline (P) at amino acid position 63 to be replaced by a serine (S). 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	0.35
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;D
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.097
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.8	.;.;M
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-7.9	D;D;D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D;T;D
Sift4G	Benign	0.14	T;.;T
Polyphen		0.93, 1.0	.;P;D
Vest4		0.83
MutPred		0.45		Gain of glycosylation at P63 (P = 0.0609);Gain of glycosylation at P63 (P = 0.0609);Gain of glycosylation at P63 (P = 0.0609);
MVP		0.29
MPC		0.053
ClinPred		1.0	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.73
gMVP		0.32

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: chr7-1195184;