NM_182976.4:c.370G>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182976.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF326	NM_182976.4	MANE Select	c.370G>A	p.Gly124Ser	missense	Exon 5 of 12	NP_892021.1	Q5BKZ1-1
	ZNF326	NM_001320185.2		c.210-107G>A		intron	N/A	NP_001307114.1	A0A0A0MRN4
	ZNF326	NM_181781.4		c.-4+2413G>A		intron	N/A	NP_861446.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF326	ENST00000340281.9	TSL:1 MANE Select	c.370G>A	p.Gly124Ser	missense	Exon 5 of 12	ENSP00000340796.4	Q5BKZ1-1
	ZNF326	ENST00000370447.3	TSL:1	c.210-107G>A		intron	N/A	ENSP00000359476.2	A0A0A0MRN4
	ZNF326	ENST00000394583.7	TSL:1	n.151+2413G>A		intron	N/A	ENSP00000378084.3	E2QRN4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		5.6
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
Mutation Taster		=67/33	polymorphism

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

Other links and lift over

hg19: chr1-90473064; COSMIC: COSV61036973; COSMIC: COSV61036973;