rs201998501

Variant names:

• chr18-74632203-T-C
• NM_017757.3:c.1184T>C

Your query was ambiguous. Multiple possible variants found:

• chr18-74632203-T-C
• chr18-74632203-T-G

Variant summary

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

The NM_017757.3(ZNF407):​c.1184T>C​(p.Leu395Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,654 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZNF407 NM_017757.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

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=0.029001594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF407	NM_017757.3	c.1184T>C	p.Leu395Ser	missense_variant	Exon 2 of 9	ENST00000299687.10	NP_060227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF407	ENST00000299687.10	c.1184T>C	p.Leu395Ser	missense_variant	Exon 2 of 9	1	NM_017757.3	ENSP00000299687.4
ZNF407	ENST00000577538.5	c.1184T>C	p.Leu395Ser	missense_variant	Exon 1 of 7	2		ENSP00000463270.1
ZNF407	ENST00000309902.10	c.1184T>C	p.Leu395Ser	missense_variant	Exon 1 of 4	2		ENSP00000310359.5
ZNF407	ENST00000582337.5	c.1184T>C	p.Leu395Ser	missense_variant	Exon 2 of 5	5		ENSP00000462348.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461654 Hom.: 0 Cov.: 55 AF XY: 0.00000413 AC XY: 3 AN XY: 727100

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: 0.00000360

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	0.098
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.42
DEOGEN2	Benign	0.021	.;.;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.45	.;T;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.029	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.81	L;L;L;L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.070	.;N;.;N
REVEL	Benign	0.054
Sift	Benign	0.78	.;T;.;T
Sift4G	Benign	0.56	T;T;T;T
Polyphen		0.0030	B;B;B;B
Vest4		0.047
MutPred		0.13		Gain of phosphorylation at L395 (P = 0.0465);Gain of phosphorylation at L395 (P = 0.0465);Gain of phosphorylation at L395 (P = 0.0465);Gain of phosphorylation at L395 (P = 0.0465);
MVP		0.043
MPC		0.12
ClinPred		0.018	T
GERP RS		0.029
Varity_R		0.028
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-72344159;