rs17056248

chr18-75063458-G-Achr18-75063458-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017757.3(ZNF407):c.5737G>A(p.Ala1913Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000448 in 1,606,410 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. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: ZNF407 NM_017757.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.955

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05147794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF407	NM_017757.3	c.5737G>A	p.Ala1913Thr	missense_variant	9/9	ENST00000299687.10
ZNF407	NM_001384475.1	c.5737G>A	p.Ala1913Thr	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF407	ENST00000299687.10	c.5737G>A	p.Ala1913Thr	missense_variant	9/9	1	NM_017757.3	P2
ZNF407	ENST00000579200.1	n.2177G>A		non_coding_transcript_exon_variant	1/1
ZNF407	ENST00000582214.1	n.455G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152114 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000217 AC: 5 AN: 230160 Hom.: 0 AF XY: 0.0000317 AC XY: 4 AN XY: 126166

Gnomad AFR exome AF: 0.000224

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: 0.0000519

Gnomad NFE exome AF: 0.00000973

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000371 AC: 54 AN: 1454296 Hom.: 0 Cov.: 29 AF XY: 0.0000277 AC XY: 20 AN XY: 723054

Gnomad4 AFR exome AF: 0.000360

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.0000508

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000196

Gnomad4 NFE exome AF: 0.0000324

Gnomad4 OTH exome AF: 0.0000333

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152114 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74286

Gnomad4 AFR AF: 0.000362

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000136

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.00000827 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 26, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	7.7
Dann	Benign	0.92
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.49	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.064
Sift	Benign	0.23	T
Sift4G	Benign	0.61	T
Polyphen		0.26	B
Vest4		0.031
MVP		0.15
MPC		0.14
ClinPred		0.021	T
GERP RS		0.74
Varity_R		0.029
gMVP		0.65

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: rs17056248; hg19: chr18-72775414;