rs749815984

Variant names:

• chr20-59191317-C-A
• rs749815984
• NM_178457.3:c.298C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-59191317-C-A
• chr20-59191317-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178457.3(ZNF831):​c.298C>A​(p.Pro100Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,124 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P100S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF831 NM_178457.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078143865).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178457.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF831	NM_178457.3	MANE Select	c.298C>A	p.Pro100Thr	missense	Exon 2 of 6	NP_848552.1	Q5JPB2
	ZNF831	NM_001384354.1		c.298C>A	p.Pro100Thr	missense	Exon 4 of 8	NP_001371283.1	Q5JPB2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF831	ENST00000371030.4	TSL:1 MANE Select	c.298C>A	p.Pro100Thr	missense	Exon 2 of 6	ENSP00000360069.2	Q5JPB2
	ZNF831	ENST00000637017.1	TSL:5	c.298C>A	p.Pro100Thr	missense	Exon 4 of 8	ENSP00000490240.1	Q5JPB2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1446124 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 718294

African (AFR) AF: 0.00 AC: 0 AN: 33052

American (AMR) AF: 0.00 AC: 0 AN: 42862

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25520

East Asian (EAS) AF: 0.00 AC: 0 AN: 38970

South Asian (SAS) AF: 0.00 AC: 0 AN: 84608

European-Finnish (FIN) AF: 0.0000196 AC: 1 AN: 51094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1104600

Other (OTH) AF: 0.00 AC: 0 AN: 59686

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.92
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.49
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.050
Sift	Benign	0.32	T
Sift4G	Benign	0.43	T
Polyphen		0.39	B
Vest4		0.13
MutPred		0.21		Gain of catalytic residue at P100 (P = 0.0404)
MVP		0.030
MPC		0.46
ClinPred		0.23	T
GERP RS		4.5
Varity_R		0.085
gMVP		0.40
Mutation Taster		=95/5	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: rs749815984; hg19: chr20-57766372;