rs748778876

Variant names:

• chr19-8511796-G-A
• rs748778876
• NM_001146175.2:c.695C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-8511796-G-A
• chr19-8511796-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001146175.2(ZNF414):​c.695C>T​(p.Pro232Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000262 in 1,409,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: ZNF414 NM_001146175.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79
• Publications: 0 publications found

Genes affected

ZNF414 (HGNC:20630): (zinc finger protein 414) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005714059).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146175.2. 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
	ZNF414	NM_001146175.2	MANE Select	c.695C>T	p.Pro232Leu	missense	Exon 5 of 8	NP_001139647.1	Q96IQ9-2
	ZNF414	NM_032370.3		c.695C>T	p.Pro232Leu	missense	Exon 5 of 6	NP_115746.2	Q96IQ9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF414	ENST00000393927.9	TSL:1 MANE Select	c.695C>T	p.Pro232Leu	missense	Exon 5 of 8	ENSP00000377504.3	Q96IQ9-2
	ZNF414	ENST00000255616.8	TSL:1	c.695C>T	p.Pro232Leu	missense	Exon 5 of 6	ENSP00000255616.7	Q96IQ9-1
	ZNF414	ENST00000593661.5	TSL:3	c.233C>T	p.Pro78Leu	missense	Exon 3 of 5	ENSP00000473079.1	M0R398

Frequencies

GnomAD3 genomes AF: 0.000526 AC: 80 AN: 152170 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000668 AC: 31 AN: 46382 AF XY: 0.000653

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00331

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000466

Gnomad OTH exome AF: 0.000986

GnomAD4 exome AF: 0.000231 AC: 290 AN: 1257706 Hom.: 0 Cov.: 42 AF XY: 0.000211 AC XY: 129 AN XY: 610816

African (AFR) AF: 0.00 AC: 0 AN: 25090

American (AMR) AF: 0.00258 AC: 39 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17342

East Asian (EAS) AF: 0.00 AC: 0 AN: 30830

South Asian (SAS) AF: 0.00 AC: 0 AN: 58206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31724

Middle Eastern (MID) AF: 0.000462 AC: 2 AN: 4330

European-Non Finnish (NFE) AF: 0.000227 AC: 232 AN: 1023098

Other (OTH) AF: 0.000327 AC: 17 AN: 51948

GnomAD4 genome AF: 0.000525 AC: 80 AN: 152278 Hom.: 0 Cov.: 34 AF XY: 0.000470 AC XY: 35 AN XY: 74448

African (AFR) AF: 0.000120 AC: 5 AN: 41580

American (AMR) AF: 0.00399 AC: 61 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000177 AC: 12 AN: 67986

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000820

ExAC AF: 0.000286 AC: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.087
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.14	N
PhyloP100		1.8
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.050
Sift	Benign	0.25	T
Sift4G	Benign	0.078	T
Polyphen		0.0	B
Vest4		0.096
MutPred		0.33		Loss of glycosylation at P232 (P = 0.0486)
MVP		0.15
MPC		0.24
ClinPred		0.021	T
GERP RS		0.71
PromoterAI		0.012	Neutral
Varity_R		0.030
gMVP		0.42
Mutation Taster		=96/4	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: rs748778876; hg19: chr19-8576680;