1-90007596-A-G

Variant names:

• chr1-90007596-A-G
• NM_182976.4:c.461A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182976.4(ZNF326):​c.461A>G​(p.Tyr154Cys) 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)
• Consequence: ZNF326 NM_182976.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.72

Genes affected

ZNF326 (HGNC:14104): (zinc finger protein 326) Enables RNA polymerase II complex binding activity. Involved in regulation of DNA-templated transcription, elongation and regulation of RNA splicing. Located in nucleoplasm. Part of DBIRD complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4122504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF326	NM_182976.4	c.461A>G	p.Tyr154Cys	missense_variant	Exon 5 of 12	ENST00000340281.9	NP_892021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF326	ENST00000340281.9	c.461A>G	p.Tyr154Cys	missense_variant	Exon 5 of 12	1	NM_182976.4	ENSP00000340796.4
ZNF326	ENST00000370447.3	c.210-16A>G		intron_variant	Intron 4 of 11	1		ENSP00000359476.2
ZNF326	ENST00000394583.7	n.152-2492A>G		intron_variant	Intron 3 of 9	1		ENSP00000378084.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.461A>G (p.Y154C) alteration is located in exon 5 (coding exon 5) of the ZNF326 gene. This alteration results from a A to G substitution at nucleotide position 461, causing the tyrosine (Y) at amino acid position 154 to be replaced by a cysteine (C). 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	0.20
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.14
Sift	Benign	0.052	T
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.25		Loss of phosphorylation at Y154 (P = 0.0146);
MVP		0.043
MPC		1.1
ClinPred		0.77	D
GERP RS		5.7
Varity_R		0.16
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr1-90473155;