chr19-44327503-C-G

Variant names:

• chr19-44327503-C-G
• rs763281425
• NM_013380.4:c.2654G>C

Variant summary

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

The NM_013380.4(ZNF112):​c.2654G>C​(p.Ser885Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S885N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: ZNF112 NM_013380.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

Genes affected

ZNF112 (HGNC:12892): (zinc finger protein 112) Predicted to enable DNA-binding transcription activator 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=0.070313096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF112	NM_013380.4	c.2654G>C	p.Ser885Thr	missense_variant	Exon 4 of 4	ENST00000354340.9	NP_037512.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF112	ENST00000354340.9	c.2654G>C	p.Ser885Thr	missense_variant	Exon 4 of 4	1	NM_013380.4	ENSP00000346305.3
ZNF112	ENST00000337401.8	c.2672G>C	p.Ser891Thr	missense_variant	Exon 5 of 5	1		ENSP00000337081.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250818 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135566

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461642 Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6 AN XY: 727120

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: 0.00000899

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.2
DANN	Benign	0.75
DEOGEN2	Benign	0.0031	.;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.28	T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.070	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.76	.;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.71	N;N
REVEL	Benign	0.063
Sift	Benign	0.38	T;T
Sift4G	Benign	0.099	T;T
Polyphen		0.0020	.;B
Vest4		0.14
MVP		0.15
MPC		0.11
ClinPred		0.040	T
GERP RS		-1.7
Varity_R		0.041
gMVP		0.083

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: rs763281425; hg19: chr19-44831656;