rs560840757

Variant names:

• chr16-72787446-G-A
• rs560840757
• NM_006885.4:c.10830C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-72787446-G-A
• chr16-72787446-G-C
• chr16-72787446-G-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006885.4(ZFHX3):​c.10830C>T​(p.Pro3610Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,453,462 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. Synonymous variant affecting the same amino acid position (i.e. P3610P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZFHX3 NM_006885.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173
• Publications: 0 publications found

Genes affected

ZFHX3 (HGNC:777): (zinc finger homeobox 3) This gene encodes a transcription factor with multiple homeodomains and zinc finger motifs, and regulates myogenic and neuronal differentiation. The encoded protein suppresses expression of the alpha-fetoprotein gene by binding to an AT-rich enhancer motif. The protein has also been shown to negatively regulate c-Myb, and transactivate the cell cycle inhibitor cyclin-dependent kinase inhibitor 1A (also known as p21CIP1). This gene is reported to function as a tumor suppressor in several cancers, and sequence variants of this gene are also associated with atrial fibrillation. Multiple transcript variants expressed from alternate promoters and encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ZFHX3-AS1 (HGNC:56033): (ZFHX3 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=0.173 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006885.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFHX3	NM_006885.4	MANE Select	c.10830C>T	p.Pro3610Pro	synonymous	Exon 10 of 10	NP_008816.3
	ZFHX3	NM_001386735.1		c.10830C>T	p.Pro3610Pro	synonymous	Exon 17 of 17	NP_001373664.1	Q15911-1
	ZFHX3	NM_001164766.2		c.8088C>T	p.Pro2696Pro	synonymous	Exon 9 of 9	NP_001158238.1	Q15911-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFHX3	ENST00000268489.10	TSL:1 MANE Select	c.10830C>T	p.Pro3610Pro	synonymous	Exon 10 of 10	ENSP00000268489.5	Q15911-1
	ZFHX3	ENST00000397992.5	TSL:1	c.8088C>T	p.Pro2696Pro	synonymous	Exon 9 of 9	ENSP00000438926.3	Q15911-2
	ZFHX3	ENST00000641206.2		c.10830C>T	p.Pro3610Pro	synonymous	Exon 18 of 18	ENSP00000493252.1	Q15911-1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD2 exomes AF: 0.00000423 AC: 1 AN: 236416 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000301

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1453462 Hom.: 0 Cov.: 37 AF XY: 0.00000277 AC XY: 2 AN XY: 721878

African (AFR) AF: 0.00 AC: 0 AN: 33376

American (AMR) AF: 0.0000452 AC: 2 AN: 44244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25932

East Asian (EAS) AF: 0.00 AC: 0 AN: 39472

South Asian (SAS) AF: 0.00 AC: 0 AN: 85706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106626

Other (OTH) AF: 0.00 AC: 0 AN: 60008

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.6
DANN	Benign	0.94
PhyloP100		0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs560840757; hg19: chr16-72821345;