10-96156611-A-T

Position:

• chr10-96156611-A-T

Variant summary

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

The NM_001330736.2(ZNF518A):​c.289A>T​(p.Thr97Ser) 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: 0.639

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=0.073789656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF518A	NM_001330736.2	c.289A>T	p.Thr97Ser	missense_variant	6/6	ENST00000316045.10	NP_001317665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF518A	ENST00000316045.10	c.289A>T	p.Thr97Ser	missense_variant	6/6	1	NM_001330736.2	ENSP00000479684	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

Feb 15, 2023

The c.289A>T (p.T97S) alteration is located in exon 6 (coding exon 1) of the ZNF518A gene. This alteration results from a A to T substitution at nucleotide position 289, causing the threonine (T) at amino acid position 97 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
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	2.3
DANN	Benign	0.79
DEOGEN2	Benign	0.0043	T;T;T;T
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.20	.;T;.;T
MetaRNN	Benign	0.074	T;T;T;T
MutationAssessor	Benign	0.41	N;.;N;N
PrimateAI	Benign	0.24	T
Sift4G	Benign	0.75	T;T;T;T
Polyphen		0.0020	B;.;B;B
Vest4		0.057
MVP		0.14
GERP RS		1.1
Varity_R		0.033
gMVP		0.13

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: chr10-97916368;