rs2277138

Variant names:

• chr8-134610397-T-A
• rs2277138
• NM_020863.4:c.634+73A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-134610397-T-A
• chr8-134610397-T-C
• chr8-134610397-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020863.4(ZFAT):​c.634+73A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000751 in 1,331,532 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: ZFAT NM_020863.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFAT	NM_020863.4	c.634+73A>T		intron_variant	Intron 4 of 15	ENST00000377838.8	NP_065914.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFAT	ENST00000377838.8	c.634+73A>T		intron_variant	Intron 4 of 15	1	NM_020863.4	ENSP00000367069.3
ZFAT	ENST00000429442.6	c.598+73A>T		intron_variant	Intron 4 of 15	1		ENSP00000394501.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.51e-7 AC: 1 AN: 1331532 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 656074

African (AFR) AF: 0.00 AC: 0 AN: 29504

American (AMR) AF: 0.00 AC: 0 AN: 26886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20590

East Asian (EAS) AF: 0.00 AC: 0 AN: 38138

South Asian (SAS) AF: 0.00 AC: 0 AN: 69066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5186

European-Non Finnish (NFE) AF: 9.64e-7 AC: 1 AN: 1037726

Other (OTH) AF: 0.00 AC: 0 AN: 55178

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 959

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.70
PhyloP100		-0.081

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

Other links and lift over

dbSNP: rs2277138; hg19: chr8-135622640;