1-90007505-G-A

Variant names:

• chr1-90007505-G-A
• NM_182976.4:c.370G>A

Variant summary

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

The NM_182976.4(ZNF326):​c.370G>A​(p.Gly124Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 5.58

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 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
ZNF326	NM_182976.4	c.370G>A	p.Gly124Ser	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.370G>A	p.Gly124Ser	missense_variant	Exon 5 of 12	1	NM_182976.4	ENSP00000340796.4
ZNF326	ENST00000370447.3	c.210-107G>A		intron_variant	Intron 4 of 11	1		ENSP00000359476.2
ZNF326	ENST00000394583.7	n.151+2413G>A		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 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.370G>A (p.G124S) alteration is located in exon 5 (coding exon 5) of the ZNF326 gene. This alteration results from a G to A substitution at nucleotide position 370, causing the glycine (G) at amino acid position 124 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	Benign	0.19
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.18
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.028	D
Polyphen		0.95	P
Vest4		0.75
MutPred		0.18		Gain of phosphorylation at G124 (P = 0.0209);
MVP		0.13
MPC		0.98
ClinPred		0.67	D
GERP RS		5.8
Varity_R		0.12
gMVP		0.39

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: chr1-90473064; COSMIC: COSV61036973; COSMIC: COSV61036973;