8-134565373-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020863.4(ZFAT):c.2936C>T(p.Pro979Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZFAT NM_020863.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.41

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFAT	NM_020863.4	c.2936C>T	p.Pro979Leu	missense_variant	11/16	ENST00000377838.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFAT	ENST00000377838.8	c.2936C>T	p.Pro979Leu	missense_variant	11/16	1	NM_020863.4	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.2936C>T (p.P979L) alteration is located in exon 11 (coding exon 11) of the ZFAT gene. This alteration results from a C to T substitution at nucleotide position 2936, causing the proline (P) at amino acid position 979 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
Cadd	Pathogenic	26
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.067	T;.;.;D;.;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.93	D;.;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.74	D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.0	D;D;D;D;D;D
REVEL	Benign	0.23
Sift	Benign	0.069	T;T;T;T;T;T
Sift4G	Benign	0.074	T;T;T;T;T;T
Polyphen		0.99	D;.;.;D;.;.
Vest4		0.73
MutPred		0.56		.;.;.;Gain of stability (P = 0.0068);.;.;
MVP		0.34
MPC		0.91
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.14
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-135577616;