18-75063458-G-C

Variant names:

• chr18-75063458-G-C
• rs17056248
• NM_017757.3:c.5737G>C

Variant summary

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

The NM_017757.3(ZNF407):​c.5737G>C​(p.Ala1913Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1913T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF407 NM_017757.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 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=0.24101394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF407	NM_017757.3	c.5737G>C	p.Ala1913Pro	missense_variant	Exon 9 of 9	ENST00000299687.10	NP_060227.2
ZNF407	NM_001384475.1	c.5737G>C	p.Ala1913Pro	missense_variant	Exon 9 of 9		NP_001371404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF407	ENST00000299687.10	c.5737G>C	p.Ala1913Pro	missense_variant	Exon 9 of 9	1	NM_017757.3	ENSP00000299687.4
ZNF407	ENST00000579200.1	n.2177G>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
ZNF407	ENST00000582214.1	n.455G>C		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000434 AC: 1 AN: 230160 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 126166

Gnomad AFR exome AF: 0.0000746

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: 0.00000138 AC: 2 AN: 1454296 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 723054

Gnomad4 AFR exome AF: 0.0000599

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.032	T
Eigen	Benign	0.058
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.13
Sift	Benign	0.038	D
Sift4G	Uncertain	0.037	D
Polyphen		1.0	D
Vest4		0.20
MutPred		0.32		Gain of disorder (P = 0.0696);
MVP		0.35
MPC		0.60
ClinPred		0.17	T
GERP RS		0.74
Varity_R		0.12
gMVP		0.88

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;