22-35265058-TC-CT

Variant names:

• chr22-35265058-TC-CT
• NM_001003681.3:c.670_671delTCinsCT
• HMGXB4 p.Ser224Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001003681.3(HMGXB4):​c.670_671delTCinsCT​(p.Ser224Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: HMGXB4 NM_001003681.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.72
• Publications: 0 publications found

Genes affected

HMGXB4 (HGNC:5003): (HMG-box containing 4) High mobility group (HMG) proteins are nonhistone chromosomal proteins. See HMG2 (MIM 163906) for additional information on HMG proteins.[supplied by OMIM, Nov 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003681.3. 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
	HMGXB4	NM_001003681.3	MANE Select	c.670_671delTCinsCT	p.Ser224Leu	missense	N/A	NP_001003681.1	Q9UGU5
	HMGXB4	NM_001362972.2		c.343_344delTCinsCT	p.Ser115Leu	missense	N/A	NP_001349901.1
	HMGXB4	NR_027780.2		n.918_919delTCinsCT		non_coding_transcript_exon	Exon 6 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGXB4	ENST00000216106.6	TSL:5 MANE Select	c.670_671delTCinsCT	p.Ser224Leu	missense	N/A	ENSP00000216106.5	Q9UGU5
	HMGXB4	ENST00000455359.5	TSL:1	c.343_344delTCinsCT	p.Ser115Leu	missense	N/A	ENSP00000415500.1	B0QXZ8
	HMGXB4	ENST00000418170.5	TSL:1	n.*506_*507delTCinsCT		non_coding_transcript_exon	Exon 6 of 12	ENSP00000395532.1	F8WDU7

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-35661051;