chr10-96157193-G-A

Position:

• chr10-96157193-G-A

Variant summary

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

The NM_001330736.2(ZNF518A):​c.871G>A​(p.Ala291Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,652 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: 0.0000034 (0 hom.)
• Consequence: ZNF518A NM_001330736.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.24

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=0.11068389).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF518A	NM_001330736.2	c.871G>A	p.Ala291Thr	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.871G>A	p.Ala291Thr	missense_variant	6/6	1	NM_001330736.2	ENSP00000479684	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000207 AC: 5 AN: 241552 Hom.: 0 AF XY: 0.0000229 AC XY: 3 AN XY: 131082

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000149

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1458652 Hom.: 0 Cov.: 32 AF XY: 0.00000414 AC XY: 3 AN XY: 725342

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000114

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000414 AC: 5

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

Nov 30, 2022

The c.871G>A (p.A291T) alteration is located in exon 6 (coding exon 1) of the ZNF518A gene. This alteration results from a G to A substitution at nucleotide position 871, causing the alanine (A) at amino acid position 291 to be replaced by a threonine (T). 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	0.20
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Benign	0.82
DEOGEN2	Benign	0.037	T;T;T;T
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	.;T;.;T
MetaRNN	Benign	0.11	T;T;T;T
MutationAssessor	Uncertain	2.1	M;.;M;M
PrimateAI	Uncertain	0.52	T
Sift4G	Benign	0.22	T;T;T;T
Polyphen		0.91	P;.;P;P
Vest4		0.35
MVP		0.26
GERP RS		5.7
Varity_R		0.11
gMVP		0.086

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

LitVar

Other links and lift over

dbSNP: rs782747998; hg19: chr10-97916950;