18-35376967-A-C

Variant names:

• chr18-35376967-A-C
• rs116303449
• NM_001322286.2:c.-73+311T>G

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.-73+311T>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF396 NM_001322286.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.764
• Publications: 5 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 (BayesDel_noAF=-0.9).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF396	NM_001322286.2	MANE Select	c.-73+311T>G		intron	N/A	NP_001309215.1
	ZNF396	NM_001322290.2		c.-310+311T>G		intron	N/A	NP_001309219.1
	ZNF396	NM_145756.3		c.-73+311T>G		intron	N/A	NP_665699.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF396	ENST00000589332.7	TSL:1 MANE Select	c.-73+311T>G		intron	N/A	ENSP00000466500.1
	ZNF396	ENST00000306346.5	TSL:1	c.-73+311T>G		intron	N/A	ENSP00000302310.1
	ZNF396	ENST00000586687.5	TSL:1	c.-73+311T>G		intron	N/A	ENSP00000467275.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.14
PhyloP100		-0.76
PromoterAI		0.044	Neutral

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: rs116303449; hg19: chr18-32956931;