rs17195211

Variant names:

• chr16-49638923-G-A
• rs17195211
• NM_001379286.1:c.302-49C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001379286.1(ZNF423):​c.302-49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 1,541,870 control chromosomes in the GnomAD database, including 1,131 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.026 (96 hom., cov: 33)
  • Exomes 𝑓: 0.036 (1035 hom.)
• Consequence: ZNF423 NM_001379286.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.47
• Publications: 4 publications found

Genes affected

ZNF423 (HGNC:16762): (zinc finger protein 423) The protein encoded by this gene is a nuclear protein that belongs to the family of Kruppel-like C2H2 zinc finger proteins. It functions as a DNA-binding transcription factor by using distinct zinc fingers in different signaling pathways. Thus, it is thought that this gene may have multiple roles in signal transduction during development. Mutations in this gene are associated with nephronophthisis-14 and Joubert syndrome-19. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2012]

ZNF423 Gene-Disease associations (from GenCC):

• nephronophthisis 14

  Inheritance: Unknown, AD, AR Classification: STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• ciliopathy

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• Joubert syndrome with oculorenal defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nephronophthisis 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0263 (4009/152318) while in subpopulation NFE AF = 0.0449 (3051/68024). AF 95% confidence interval is 0.0435. There are 96 homozygotes in GnomAd4. There are 1839 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 96 AD,Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379286.1. 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
	ZNF423	NM_001379286.1	MANE Select	c.302-49C>T		intron	N/A	NP_001366215.1	A0A7P0Q1F0
	ZNF423	NM_015069.5		c.278-49C>T		intron	N/A	NP_055884.2
	ZNF423	NM_001271620.2		c.98-49C>T		intron	N/A	NP_001258549.1	Q2M1K9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF423	ENST00000563137.7	TSL:5 MANE Select	c.302-49C>T		intron	N/A	ENSP00000455588.3	A0A7P0Q1F0
	ZNF423	ENST00000562520.1	TSL:1	c.98-49C>T		intron	N/A	ENSP00000457664.1	Q2M1K9-2
	ZNF423	ENST00000567169.5	TSL:1	c.-74-49C>T		intron	N/A	ENSP00000455061.1	F5H7S1

Frequencies

GnomAD3 genomes AF: 0.0263 AC: 4009 AN: 152200 Hom.: 96 Cov.: 33

Gnomad AFR AF: 0.00620

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.0380

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.0325

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0448

Gnomad OTH AF: 0.0191

GnomAD2 exomes AF: 0.0255 AC: 4490 AN: 176082 AF XY: 0.0259

Gnomad AFR exome AF: 0.00587

Gnomad AMR exome AF: 0.00457

Gnomad ASJ exome AF: 0.0370

Gnomad EAS exome AF: 0.000775

Gnomad FIN exome AF: 0.0325

Gnomad NFE exome AF: 0.0417

Gnomad OTH exome AF: 0.0225

GnomAD4 exome AF: 0.0359 AC: 49922 AN: 1389552 Hom.: 1035 Cov.: 35 AF XY: 0.0355 AC XY: 24194 AN XY: 682004

African (AFR) AF: 0.00528 AC: 168 AN: 31814

American (AMR) AF: 0.00538 AC: 203 AN: 37760

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 804 AN: 21816

East Asian (EAS) AF: 0.000496 AC: 19 AN: 38338

South Asian (SAS) AF: 0.0148 AC: 1087 AN: 73608

European-Finnish (FIN) AF: 0.0313 AC: 1531 AN: 48938

Middle Eastern (MID) AF: 0.00531 AC: 29 AN: 5462

European-Non Finnish (NFE) AF: 0.0415 AC: 44540 AN: 1074470

Other (OTH) AF: 0.0269 AC: 1541 AN: 57346

GnomAD4 genome AF: 0.0263 AC: 4009 AN: 152318 Hom.: 96 Cov.: 33 AF XY: 0.0247 AC XY: 1839 AN XY: 74468

African (AFR) AF: 0.00618 AC: 257 AN: 41574

American (AMR) AF: 0.00771 AC: 118 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0380 AC: 132 AN: 3472

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5174

South Asian (SAS) AF: 0.00933 AC: 45 AN: 4824

European-Finnish (FIN) AF: 0.0325 AC: 345 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0449 AC: 3051 AN: 68024

Other (OTH) AF: 0.0189 AC: 40 AN: 2114

Alfa AF: 0.0360 Hom.: 65

Bravo AF: 0.0224

Asia WGS AF: 0.00520 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Benign	0.88
PhyloP100		3.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs17195211; hg19: chr16-49672834;