chr22-35265152-C-T

Position:

• chr22-35265152-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001003681.3(HMGXB4):​c.764C>T​(p.Ser255Phe) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: HMGXB4 NM_001003681.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.986

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]

HMGXB4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11621195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGXB4	NM_001003681.3	c.764C>T	p.Ser255Phe	missense_variant	5/11	ENST00000216106.6	NP_001003681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGXB4	ENST00000216106.6	c.764C>T	p.Ser255Phe	missense_variant	5/11	5	NM_001003681.3	ENSP00000216106.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 31

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

Jan 12, 2024

The c.764C>T (p.S255F) alteration is located in exon 5 (coding exon 4) of the HMGXB4 gene. This alteration results from a C to T substitution at nucleotide position 764, causing the serine (S) at amino acid position 255 to be replaced by a phenylalanine (F). 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	Benign	0.088
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.075	T;.;T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.026
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.5	.;.;L
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.052
Sift	Uncertain	0.012	D;D;D
Sift4G	Uncertain	0.049	D;D;D
Polyphen		0.61	.;.;P
Vest4		0.22
MutPred		0.17		.;.;Loss of phosphorylation at S255 (P = 0.0054);
MVP		0.44
MPC		0.11
ClinPred		0.41	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.064
gMVP		0.12

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: chr22-35661145; COSMIC: COSV53332695; COSMIC: COSV53332695;