8-134610397-T-C

Position:

• chr8-134610397-T-C

Variant summary

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

The NM_020863.4(ZFAT):​c.634+73A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,481,682 control chromosomes in the GnomAD database, including 125,932 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 0.40 (12637 hom., cov: 32)
  • Exomes 𝑓: 0.41 (113295 hom.)
• Consequence: ZFAT NM_020863.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

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]

ZFAT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFAT	NM_020863.4	c.634+73A>G		intron_variant		ENST00000377838.8	NP_065914.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFAT	ENST00000377838.8	c.634+73A>G		intron_variant		1	NM_020863.4	ENSP00000367069.3
ZFAT	ENST00000429442.6	c.598+73A>G		intron_variant		1		ENSP00000394501.2

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60458 AN: 151968 Hom.: 12622 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.397

GnomAD4 exome AF: 0.409 AC: 543582 AN: 1329596 Hom.: 113295 AF XY: 0.410 AC XY: 268702 AN XY: 655144

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.611

Gnomad4 ASJ exome AF: 0.336

Gnomad4 EAS exome AF: 0.537

Gnomad4 SAS exome AF: 0.496

Gnomad4 FIN exome AF: 0.498

Gnomad4 NFE exome AF: 0.394

Gnomad4 OTH exome AF: 0.408

GnomAD4 genome AF: 0.398 AC: 60502 AN: 152086 Hom.: 12637 Cov.: 32 AF XY: 0.408 AC XY: 30346 AN XY: 74338

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.400

Alfa AF: 0.287 Hom.: 921

Bravo AF: 0.394

Asia WGS AF: 0.523 AC: 1818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.2
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2277138; hg19: chr8-135622640; COSMIC: COSV64735889;