NM_198535.3:c.1228A>T

Variant names:

• chr19-9296176-T-A
• NM_198535.3:c.1228A>T

Variant summary

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

The NM_198535.3(ZNF699):​c.1228A>T​(p.Met410Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ZNF699 NM_198535.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.468

Genes affected

ZNF699 (HGNC:24750): (zinc finger protein 699) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.07490787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF699	NM_198535.3	c.1228A>T	p.Met410Leu	missense_variant	Exon 6 of 6	ENST00000591998.6	NP_940937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF699	ENST00000591998.6	c.1228A>T	p.Met410Leu	missense_variant	Exon 6 of 6	5	NM_198535.3	ENSP00000467723.1
ZNF699	ENST00000308650.4	c.1228A>T	p.Met410Leu	missense_variant	Exon 5 of 5	1		ENSP00000311596.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461816 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727198

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: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.89
DEOGEN2	Benign	0.050	T;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.29	.;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.85	.;N
REVEL	Benign	0.039
Sift	Benign	0.13	.;T
Sift4G	Uncertain	0.060	T;T
Polyphen		0.0050	B;B
Vest4		0.16
MutPred		0.34		Loss of ubiquitination at K412 (P = 0.0811);Loss of ubiquitination at K412 (P = 0.0811);
MVP		0.28
MPC		0.13
ClinPred		0.13	T
GERP RS		1.2
Varity_R		0.072
gMVP		0.051

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: chr19-9406852;