16-3437041-T-G

Variant names:

• chr16-3437041-T-G
• rs147050683
• NM_152457.3:c.658A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152457.3(ZNF597):​c.658A>C​(p.Ser220Arg) 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. 13/22 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. S220G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF597 NM_152457.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450
• Publications: 0 publications found

Genes affected

ZNF597 (HGNC:26573): (zinc finger protein 597) This gene encodes a protein with multiple zinc finger domains. Loss of the related gene in rodents results in defects in neural development and embryonic lethality in mutant homozygotes. This gene is adjacent to a differentially methylated region (DMR) and is imprinted and maternally expressed. [provided by RefSeq, Nov 2015]

ENSG00000285329 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3467893).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152457.3. 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
	ZNF597	NM_152457.3	MANE Select	c.658A>C	p.Ser220Arg	missense	Exon 4 of 4	NP_689670.1	Q96LX8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF597	ENST00000301744.7	TSL:1 MANE Select	c.658A>C	p.Ser220Arg	missense	Exon 4 of 4	ENSP00000301744.4	Q96LX8
	ENSG00000285329	ENST00000575785.2	TSL:4	n.212-11430T>G		intron	N/A	ENSP00000477472.1	V9GZ69

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.032	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.45
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.070
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.033	D
Polyphen		0.99	D
Vest4		0.34
MutPred		0.62		Gain of MoRF binding (P = 0.0256)
MVP		0.24
MPC		0.28
ClinPred		0.74	D
GERP RS		2.4
Varity_R		0.34
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs147050683; hg19: chr16-3487041;