7-149154239-G-T

Variant names:

• chr7-149154239-G-T
• rs982829410
• ENST00000426851.6:c.-195G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020781.4(ZNF398):​c.-195G>T variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: ZNF398 NM_020781.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.12
• Publications: 0 publications found

Genes affected

ZNF398 (HGNC:18373): (zinc finger protein 398) This gene encodes a member of the Kruppel family of C2H2-type zinc-finger transcription factor proteins. The encoded protein acts as a transcriptional activator. Two transcript variants encoding distinct isoforms have been identified for this gene. Other transcript variants have been described, but their full length sequence has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.842

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020781.4. 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
	ZNF398	NM_170686.3	MANE Select	c.319G>T	p.Gly107Trp	missense	Exon 2 of 6	NP_733787.1	Q8TD17-1
	ZNF398	NM_020781.4		c.-195G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 7	NP_065832.1	Q8TD17-2
	ZNF398	NM_020781.4		c.-195G>T		5_prime_UTR	Exon 3 of 7	NP_065832.1	Q8TD17-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF398	ENST00000426851.6	TSL:1	c.-195G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 7	ENSP00000389972.2	Q8TD17-2
	ZNF398	ENST00000475153.6	TSL:1 MANE Select	c.319G>T	p.Gly107Trp	missense	Exon 2 of 6	ENSP00000420418.1	Q8TD17-1
	ZNF398	ENST00000426851.6	TSL:1	c.-195G>T		5_prime_UTR	Exon 3 of 7	ENSP00000389972.2	Q8TD17-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	1.9	L
PhyloP100		4.1
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-7.2	D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.68
MVP		0.83
MPC		1.1
ClinPred		0.99	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.72
gMVP		0.79
Mutation Taster		=62/38	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: rs982829410; hg19: chr7-148851331;