18-35374205-C-G

Variant names:

• chr18-35374205-C-G
• rs778576252
• NM_001322286.2:c.88G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001322286.2(ZNF396):​c.88G>C​(p.Glu30Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E30K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF396 NM_001322286.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110
• Publications: 0 publications found

Genes affected

ZNF396 (HGNC:18824): (zinc finger protein 396) Enables protein heterodimerization activity; protein homodimerization activity; and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription, DNA-templated. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061122835).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322286.2. 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
	ZNF396	NM_001322286.2	MANE Select	c.88G>C	p.Glu30Gln	missense	Exon 2 of 4	NP_001309215.1	Q96N95-1
	ZNF396	NM_001322290.2		c.88G>C	p.Glu30Gln	missense	Exon 3 of 5	NP_001309219.1	Q96N95-1
	ZNF396	NM_145756.3		c.88G>C	p.Glu30Gln	missense	Exon 2 of 5	NP_665699.1	Q96N95-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF396	ENST00000589332.7	TSL:1 MANE Select	c.88G>C	p.Glu30Gln	missense	Exon 2 of 4	ENSP00000466500.1	Q96N95-1
	ZNF396	ENST00000306346.5	TSL:1	c.88G>C	p.Glu30Gln	missense	Exon 2 of 5	ENSP00000302310.1	Q96N95-3
	ZNF396	ENST00000586687.5	TSL:1	c.88G>C	p.Glu30Gln	missense	Exon 2 of 3	ENSP00000467275.1	Q96N95-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251468 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.11
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.028
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.015	D
Polyphen		0.19	B
Vest4		0.18
MutPred		0.15		Loss of phosphorylation at T33 (P = 0.1865)
MVP		0.24
MPC		0.47
ClinPred		0.56	D
GERP RS		2.1
Varity_R		0.15
gMVP		0.24
Mutation Taster		=100/0	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

dbSNP: rs778576252; hg19: chr18-32954169;