20-59192632-G-C

Variant names:

• chr20-59192632-G-C
• rs114604989
• NM_178457.3:c.1613G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178457.3(ZNF831):​c.1613G>C​(p.Gly538Ala) 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. 16/22 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. G538D) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF831 NM_178457.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 0 publications found

Genes affected

ZNF831 (HGNC:16167): (zinc finger protein 831) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03700164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF831	NM_178457.3	c.1613G>C	p.Gly538Ala	missense_variant	Exon 2 of 6	ENST00000371030.4	NP_848552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF831	ENST00000371030.4	c.1613G>C	p.Gly538Ala	missense_variant	Exon 2 of 6	1	NM_178457.3	ENSP00000360069.2
ZNF831	ENST00000637017.1	c.1613G>C	p.Gly538Ala	missense_variant	Exon 4 of 8	5		ENSP00000490240.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.11
DANN	Benign	0.11
DEOGEN2	Benign	0.00070	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.51	.;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.037	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.6	N;N
PhyloP100		1.4
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.27	.;N
REVEL	Benign	0.052
Sift	Benign	0.95	.;T
Sift4G	Benign	1.0	.;T
Polyphen		0.0	B;B
Vest4		0.045
MutPred		0.20		Loss of catalytic residue at G538 (P = 0.0418);Loss of catalytic residue at G538 (P = 0.0418);
MVP		0.030
MPC		0.22
ClinPred		0.036	T
GERP RS		3.3
Varity_R		0.025
gMVP		0.16
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs114604989; hg19: chr20-57767687;