rs193252937

Variant names:

• chr19-20948746-A-C
• rs193252937
• NM_003429.5:c.232A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-20948746-A-C
• chr19-20948746-A-G
• chr19-20948746-A-T

Variant summary

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

The NM_003429.5(ZNF85):​c.232A>C​(p.Met78Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,390,332 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. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. M78V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF85 NM_003429.5 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 0 publications found

Genes affected

ZNF85 (HGNC:13160): (zinc finger protein 85) Enables DNA-binding transcription repressor 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, DNA-templated. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000298806 (HGNC:):

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=0.07245365).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF85	NM_003429.5	c.232A>C	p.Met78Leu	missense_variant, splice_region_variant	Exon 4 of 4	ENST00000328178.13	NP_003420.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF85	ENST00000328178.13	c.232A>C	p.Met78Leu	missense_variant, splice_region_variant	Exon 4 of 4	1	NM_003429.5	ENSP00000329793.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000497 AC: 1 AN: 201364 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000611

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1390332 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 685494

African (AFR) AF: 0.00 AC: 0 AN: 30864

American (AMR) AF: 0.00 AC: 0 AN: 32510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21956

East Asian (EAS) AF: 0.0000512 AC: 2 AN: 39090

South Asian (SAS) AF: 0.00 AC: 0 AN: 71608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5446

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080574

Other (OTH) AF: 0.00 AC: 0 AN: 57338

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.13
DANN	Benign	0.40
DEOGEN2	Benign	0.0098	.;.;T;.;.;.;.;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.63	T;T;T;T;T;D;T;D;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.056	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.4	.;.;L;.;.;.;.;.;.
PhyloP100		-1.8
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	.;.;N;.;N;.;.;.;.
REVEL	Benign	0.020
Sift	Benign	0.26	.;.;T;.;T;.;.;.;.
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T;T
Polyphen		0.0, 0.059	.;.;B;.;B;.;.;.;.
Vest4		0.17, 0.25
MutPred		0.31		.;.;Loss of methylation at K74 (P = 0.0817);.;.;.;.;.;.;
MVP		0.15
MPC		0.0041
ClinPred		0.039	T
GERP RS		-2.1
Varity_R		0.048
gMVP		0.031
Mutation Taster		=97/3	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: rs193252937; hg19: chr19-21131552;