rs10505624

Variant names:

• chr8-134526437-G-C
• rs10505624
• NM_020863.4:c.3116-5436C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-134526437-G-C
• chr8-134526437-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020863.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFAT	NM_020863.4	MANE Select	c.3116-5436C>G		intron	N/A	NP_065914.2
	ZFAT	NM_001029939.4		c.3080-5436C>G		intron	N/A	NP_001025110.2
	ZFAT	NM_001167583.3		c.3080-5436C>G		intron	N/A	NP_001161055.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFAT	ENST00000377838.8	TSL:1 MANE Select	c.3116-5436C>G		intron	N/A	ENSP00000367069.3
	ZFAT	ENST00000520214.5	TSL:1	c.3080-5436C>G		intron	N/A	ENSP00000428483.1
	ZFAT	ENST00000520727.5	TSL:1	c.3080-5436C>G		intron	N/A	ENSP00000427831.1

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

African (AFR) AF: 0.0442 AC: 1833 AN: 41498

American (AMR) AF: 0.130 AC: 1994 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3468

East Asian (EAS) AF: 0.0330 AC: 171 AN: 5180

South Asian (SAS) AF: 0.140 AC: 672 AN: 4816

European-Finnish (FIN) AF: 0.206 AC: 2173 AN: 10564

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12875 AN: 67996

Other (OTH) AF: 0.131 AC: 276 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.54
PhyloP100		0.048
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: rs10505624; hg19: chr8-135538680;