rs373519575

Positions:

• chr18-74632549-C-A
• chr18-74632549-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.1530C>A​(p.Asp510Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D510D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF407 NM_017757.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.704

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]

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=0.07192859).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF407	NM_017757.3	c.1530C>A	p.Asp510Glu	missense_variant	2/9	ENST00000299687.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF407	ENST00000299687.10	c.1530C>A	p.Asp510Glu	missense_variant	2/9	1	NM_017757.3	P2
ZNF407	ENST00000577538.5	c.1530C>A	p.Asp510Glu	missense_variant	1/7	2		A2
ZNF407	ENST00000309902.10	c.1530C>A	p.Asp510Glu	missense_variant	1/4	2
ZNF407	ENST00000582337.5	c.1530C>A	p.Asp510Glu	missense_variant	2/5	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248966 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135158

Gnomad AFR exome AF: 0.0000648

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461678 Hom.: 0 Cov.: 66 AF XY: 0.00 AC XY: 0 AN XY: 727116

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.088
DANN	Benign	0.93
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.12	N
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.072	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	N;N;N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.21	T
Sift4G	Benign	0.40	T;T;T;T
Polyphen		0.039	B;B;B;B
Vest4		0.018
MutPred		0.14		Gain of glycosylation at P508 (P = 0.1007);Gain of glycosylation at P508 (P = 0.1007);Gain of glycosylation at P508 (P = 0.1007);Gain of glycosylation at P508 (P = 0.1007);
MVP		0.19
MPC		0.080
ClinPred		0.049	T
GERP RS		-4.0
Varity_R		0.054
gMVP		0.061

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: rs373519575; hg19: chr18-72344505;