19-51965437-A-C

Position:

• chr19-51965437-A-C

Variant summary

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

The NM_021632.4(ZNF350):​c.1016T>G​(p.Phe339Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF350 NM_021632.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.133

Genes affected

ZNF350 (HGNC:16656): (zinc finger protein 350) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nuclear body. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

ZNF350-AS1 (HGNC:48598): (ZNF350 antisense RNA 1)

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=0.27723098).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF350	NM_021632.4	c.1016T>G	p.Phe339Cys	missense_variant	5/5	ENST00000243644.9
ZNF350-AS1	NR_103847.1	n.103-10954A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF350	ENST00000243644.9	c.1016T>G	p.Phe339Cys	missense_variant	5/5	1	NM_021632.4	P1
ZNF350-AS1	ENST00000595010.4	n.121-10954A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

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

Dec 19, 2022

The c.1016T>G (p.F339C) alteration is located in exon 5 (coding exon 4) of the ZNF350 gene. This alteration results from a T to G substitution at nucleotide position 1016, causing the phenylalanine (F) at amino acid position 339 to be replaced by a cysteine (C). 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
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	23
DANN	Benign	0.92
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.050	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.030	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.063
Sift	Benign	0.18	T
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.39
MutPred		0.54		Loss of stability (P = 0.0481);
MVP		0.14
MPC		0.88
ClinPred		0.44	T
GERP RS		-1.5
Varity_R		0.20
gMVP		0.023

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: chr19-52468690;