rs10505624

chr8-134526437-G-Cchr8-134526437-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020863.4(ZFAT):c.3116-5436C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,116 control chromosomes in the GnomAD database, including 1,851 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 0.14 (1851 hom., cov: 33)
• Consequence: ZFAT NM_020863.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

Genes affected

ZFAT (HGNC:19899): (zinc finger and AT-hook domain containing) This gene encodes a protein that likely binds DNA and functions as a transcriptional regulator involved in apoptosis and cell survival. This gene resides in a susceptibility locus for autoimmune thyroid disease (AITD) on chromosome 8q24. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFAT	NM_020863.4	c.3116-5436C>G		intron_variant		ENST00000377838.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFAT	ENST00000377838.8	c.3116-5436C>G		intron_variant		1	NM_020863.4	P4

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20881 AN: 151998 Hom.: 1850 Cov.: 33

Gnomad AFR AF: 0.0443

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0333

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.131

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.137 AC: 20879 AN: 152116 Hom.: 1851 Cov.: 33 AF XY: 0.138 AC XY: 10247 AN XY: 74350

Gnomad4 AFR AF: 0.0442

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0330

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0899 Hom.: 157

Bravo AF: 0.126

Asia WGS AF: 0.0960 AC: 336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.6
Dann	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs10505624; hg19: chr8-135538680;