chr10-43608618-C-T

Variant names:

• chr10-43608618-C-T
• rs780534178
• NM_145312.4:c.29C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_145312.4(ZNF485):​c.29C>T​(p.Pro10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,612,978 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: ZNF485 NM_145312.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.600
• Publications: 1 publications found

Genes affected

ZNF485 (HGNC:23440): (zinc finger protein 485) 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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01270777).
• BP6: Variant 10-43608618-C-T is Benign according to our data. Variant chr10-43608618-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3196096.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145312.4. 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
	ZNF485	NM_145312.4	MANE Select	c.29C>T	p.Pro10Leu	missense	Exon 3 of 5	NP_660355.2	Q8NCK3-1
	ZNF485	NM_001318140.2		c.29C>T	p.Pro10Leu	missense	Exon 3 of 5	NP_001305069.1	Q8NCK3-1
	ZNF485	NM_001318141.2		c.29C>T	p.Pro10Leu	missense	Exon 3 of 5	NP_001305070.1	Q8NCK3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF485	ENST00000361807.8	TSL:1 MANE Select	c.29C>T	p.Pro10Leu	missense	Exon 3 of 5	ENSP00000354694.3	Q8NCK3-1
	ZNF485	ENST00000374435.3	TSL:1	c.29C>T	p.Pro10Leu	missense	Exon 3 of 5	ENSP00000363558.3	Q8NCK3-1
	ZNF485	ENST00000896014.1		c.29C>T	p.Pro10Leu	missense	Exon 2 of 4	ENSP00000566073.1

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152128 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000185 AC: 46 AN: 249142 AF XY: 0.000149

Gnomad AFR exome AF: 0.0000621

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000549

Gnomad FIN exome AF: 0.00139

Gnomad NFE exome AF: 0.0000800

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.000140 AC: 204 AN: 1460850 Hom.: 0 Cov.: 30 AF XY: 0.000128 AC XY: 93 AN XY: 726586

African (AFR) AF: 0.0000896 AC: 3 AN: 33472

American (AMR) AF: 0.0000225 AC: 1 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39682

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86106

European-Finnish (FIN) AF: 0.00103 AC: 55 AN: 53390

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.000122 AC: 136 AN: 1111456

Other (OTH) AF: 0.0000663 AC: 4 AN: 60368

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74318

African (AFR) AF: 0.0000241 AC: 1 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000848 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.0000988 AC: 12

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.97
DANN	Benign	0.89
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-1.0	N
PhyloP100		-0.60
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.053
Sift	Benign	0.41	T
Sift4G	Benign	0.81	T
Polyphen		0.47	P
Vest4		0.074
MVP		0.21
MPC		0.12
ClinPred		0.0091	T
GERP RS		-0.35
Varity_R		0.037
gMVP		0.044
Mutation Taster		=100/0	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: rs780534178; hg19: chr10-44104066;