17-42031733-C-A

Position:

• chr17-42031733-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001392013.1(ZNF385C):​c.562G>T​(p.Ala188Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,398,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ZNF385C NM_001392013.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.23

Genes affected

ZNF385C (HGNC:33722): (zinc finger protein 385C) Predicted to enable nucleic acid binding activity and zinc ion binding activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2657525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF385C	NM_001392013.1	c.562G>T	p.Ala188Ser	missense_variant	5/9	ENST00000692273.1	NP_001378942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF385C	ENST00000692273.1	c.562G>T	p.Ala188Ser	missense_variant	5/9		NM_001392013.1	ENSP00000509658.1
ZNF385C	ENST00000436535.5	c.562G>T	p.Ala188Ser	missense_variant	5/9	5		ENSP00000411514.4
ZNF385C	ENST00000649819.1	c.244G>T	p.Ala82Ser	missense_variant	3/7			ENSP00000497755.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398570 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689794

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Ambry Genetics

Jul 13, 2021

The c.325G>T (p.A109S) alteration is located in exon 4 (coding exon 4) of the ZNF385C gene. This alteration results from a G to T substitution at nucleotide position 325, causing the alanine (A) at amino acid position 109 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D;D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.3	.;N
REVEL	Benign	0.12
Sift	Benign	0.035	.;D
Sift4G	Benign	0.18	T;.
Vest4		0.49
MutPred		0.30		.;Gain of phosphorylation at A188 (P = 0.0412);
MVP		0.30
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.23
gMVP		0.25

Splicing

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: chr17-40183751;