rs769492762

Positions:

• chr18-75063422-C-G
• chr18-75063422-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017757.3(ZNF407):​c.5701C>G​(p.Arg1901Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNF407 NM_017757.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.623

Genes affected

ZNF407 (HGNC:19904): (zinc finger protein 407) This gene encodes a zinc finger protein whose exact function is not known. It may be involved in transcriptional regulation. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ZNF407 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16224179).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF407	NM_017757.3	c.5701C>G	p.Arg1901Gly	missense_variant	9/9	ENST00000299687.10	NP_060227.2
ZNF407	NM_001384475.1	c.5701C>G	p.Arg1901Gly	missense_variant	9/9		NP_001371404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF407	ENST00000299687.10	c.5701C>G	p.Arg1901Gly	missense_variant	9/9	1	NM_017757.3	ENSP00000299687.4
ZNF407	ENST00000579200.1	n.2141C>G		non_coding_transcript_exon_variant	1/1	6
ZNF407	ENST00000582214.1	n.419C>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000425 AC: 1 AN: 235204 Hom.: 0 AF XY: 0.00000775 AC XY: 1 AN XY: 129008

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000957

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457824 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725116

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.58	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.10
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.010	D
Polyphen		0.90	P
Vest4		0.16
MutPred		0.66		Gain of catalytic residue at V1902 (P = 0.0133);
MVP		0.082
MPC		0.71
ClinPred		0.82	D
GERP RS		-0.43
Varity_R		0.14
gMVP		0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs769492762; hg19: chr18-72775378;