1-90005211-T-C

Variant names:

• chr1-90005211-T-C
• NM_182976.4:c.176T>C

Variant summary

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

The NM_182976.4(ZNF326):​c.176T>C​(p.Met59Thr) 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: 30)
• Consequence: ZNF326 NM_182976.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.62

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=0.36598933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF326	NM_182976.4	c.176T>C	p.Met59Thr	missense_variant	Exon 4 of 12	ENST00000340281.9	NP_892021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF326	ENST00000340281.9	c.176T>C	p.Met59Thr	missense_variant	Exon 4 of 12	1	NM_182976.4	ENSP00000340796.4
ZNF326	ENST00000370447.3	c.176T>C	p.Met59Thr	missense_variant	Exon 4 of 12	1		ENSP00000359476.2
ZNF326	ENST00000361911.9	c.176T>C	p.Met59Thr	missense_variant	Exon 4 of 4	1		ENSP00000355318.5
ZNF326	ENST00000394583.7	n.151+119T>C		intron_variant	Intron 3 of 9	1		ENSP00000378084.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.176T>C (p.M59T) alteration is located in exon 4 (coding exon 4) of the ZNF326 gene. This alteration results from a T to C substitution at nucleotide position 176, causing the methionine (M) at amino acid position 59 to be replaced by a threonine (T). 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	0.43
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Benign	0.21	T;.;.
Eigen	Benign	-0.13
Eigen_PC	Benign	0.0078
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.87	D;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.3	N;D;N
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D;D;D
Sift4G	Benign	0.39	T;D;T
Polyphen		0.090	B;.;.
Vest4		0.74
MutPred		0.27		Loss of stability (P = 0.0041);Loss of stability (P = 0.0041);Loss of stability (P = 0.0041);
MVP		0.12
MPC		0.80
ClinPred		0.81	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.50

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: chr1-90470770;