10-96157169-A-G

Position:

• chr10-96157169-A-G

Variant summary

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

The NM_001330736.2(ZNF518A):​c.847A>G​(p.Thr283Ala) 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. 10/13 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: ZNF518A NM_001330736.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.92

Genes affected

ZNF518A (HGNC:29009): (zinc finger protein 518A) The protein encoded by this gene is a member of the krueppel C2H2-type zinc finger protein family. The encoded protein contains five zinc fingers and is likely a nuclear transcriptional regulator. Numerous transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Aug 2016]

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=0.17548248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF518A	NM_001330736.2	c.847A>G	p.Thr283Ala	missense_variant	6/6	ENST00000316045.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF518A	ENST00000316045.10	c.847A>G	p.Thr283Ala	missense_variant	6/6	1	NM_001330736.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Jan 22, 2024

The c.847A>G (p.T283A) alteration is located in exon 6 (coding exon 1) of the ZNF518A gene. This alteration results from a A to G substitution at nucleotide position 847, causing the threonine (T) at amino acid position 283 to be replaced by an alanine (A). 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	Benign	0.093
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Benign	0.87
DEOGEN2	Benign	0.016	T;T;T;T
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.54	.;T;.;T
MetaRNN	Benign	0.18	T;T;T;T
MutationAssessor	Benign	0.89	L;.;L;L
PrimateAI	Benign	0.35	T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.12	B;.;B;B
Vest4		0.20
MVP		0.22
GERP RS		4.4
Varity_R		0.16
gMVP		0.080

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: chr10-97916926;