NM_033400.3:c.-50+2214A>C

Variant names:

• chr14-23549129-T-G
• rs222682
• NM_033400.3:c.-50+2214A>C

Variant summary

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

The NM_033400.3(ZFHX2):​c.-50+2214A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 30)
• Consequence: ZFHX2 NM_033400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 4 publications found

Genes affected

ZFHX2 (HGNC:20152): (zinc finger homeobox 2) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in regulation of sensory perception of pain. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZFHX2-AS1 (HGNC:52658): (ZFHX2 antisense RNA 1)

THTPA (HGNC:18987): (thiamine triphosphatase) This gene encodes an enzyme which catalyzes the biosynthesis of thiamine disphophate (vitamin B1) by hydrolysis of thiamine triphosphate. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

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=-0.69).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033400.3. 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
	ZFHX2	NM_033400.3	MANE Select	c.-50+2214A>C		intron	N/A	NP_207646.2
	THTPA	NR_046051.1		n.466-9566T>G		intron	N/A
	THTPA	NR_046052.1		n.246-9566T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFHX2	ENST00000419474.5	TSL:5 MANE Select	c.-50+2214A>C		intron	N/A	ENSP00000413418.2
	ZFHX2	ENST00000412565.2	TSL:2	c.-50+6594A>C		intron	N/A	ENSP00000409464.2
	ZFHX2-AS1	ENST00000553985.1	TSL:2	n.239-9566T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 83664

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.77
DANN	Benign	0.84
PhyloP100		-1.1

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: rs222682; hg19: chr14-24018338;