chr22-35265152-C-T

Variant names:

• chr22-35265152-C-T
• rs1462566241
• NM_001003681.3:c.764C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• 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.

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

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.764C>T	p.Ser255Phe	missense	Exon 5 of 11	NP_001003681.1	Q9UGU5
	HMGXB4	NM_001362972.2		c.437C>T	p.Ser146Phe	missense	Exon 4 of 10	NP_001349901.1
	HMGXB4	NR_027780.2		n.1012C>T		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.764C>T	p.Ser255Phe	missense	Exon 5 of 11	ENSP00000216106.5	Q9UGU5
	HMGXB4	ENST00000455359.5	TSL:1	c.437C>T	p.Ser146Phe	missense	Exon 5 of 5	ENSP00000415500.1	B0QXZ8
	HMGXB4	ENST00000418170.5	TSL:1	n.*600C>T		non_coding_transcript_exon	Exon 6 of 12	ENSP00000395532.1	F8WDU7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.026
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.99
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.052
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.049	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
Mutation Taster		=85/15	polymorphism

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: rs1462566241; hg19: chr22-35661145; COSMIC: COSV53332695; COSMIC: COSV53332695;