chr9-72355992-C-A

Variant names:

• chr9-72355992-C-A
• rs781212359
• NM_001102420.3:c.603G>T

Variant summary

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

The NM_001102420.3(ZFAND5):​c.603G>T​(p.Glu201Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZFAND5 NM_001102420.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.502

Genes affected

ZFAND5 (HGNC:13008): (zinc finger AN1-type containing 5) Predicted to enable DNA binding activity and zinc ion binding activity. Predicted to act upstream of or within several processes, including face development; fibroblast migration; and platelet-derived growth factor receptor signaling pathway. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LINC01504 (HGNC:51185): (long intergenic non-protein coding RNA 1504)

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=0.12405726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFAND5	NM_001102420.3	c.603G>T	p.Glu201Asp	missense_variant	Exon 7 of 7	ENST00000376962.10	NP_001095890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFAND5	ENST00000376962.10	c.603G>T	p.Glu201Asp	missense_variant	Exon 7 of 7	1	NM_001102420.3	ENSP00000366161.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460430 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726516

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: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.603G>T (p.E201D) alteration is located in exon 7 (coding exon 5) of the ZFAND5 gene. This alteration results from a G to T substitution at nucleotide position 603, causing the glutamic acid (E) at amino acid position 201 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	Pathogenic	0.82
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.19	T;T;T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D;.;.;.
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L;L;L
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.063	T;T;T;T
Sift4G	Benign	0.17	T;T;T;T
Polyphen		0.058	B;B;B;B
Vest4		0.20
MutPred		0.21		Gain of ubiquitination at K197 (P = 0.102);Gain of ubiquitination at K197 (P = 0.102);Gain of ubiquitination at K197 (P = 0.102);Gain of ubiquitination at K197 (P = 0.102);
MVP		0.082
MPC		2.2
ClinPred		0.18	T
GERP RS		0.83
Varity_R		0.12
gMVP		0.86

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

LitVar

Other links and lift over

dbSNP: rs781212359; hg19: chr9-74970908;