NM_001003681.3:c.527A>C

Variant names:

• chr22-35264915-A-C
• rs760079226
• NM_001003681.3:c.527A>C

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.527A>C​(p.Tyr176Ser) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y176C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: HMGXB4 NM_001003681.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• 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=0.22778821).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGXB4	NM_001003681.3	c.527A>C	p.Tyr176Ser	missense_variant	Exon 5 of 11	ENST00000216106.6	NP_001003681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGXB4	ENST00000216106.6	c.527A>C	p.Tyr176Ser	missense_variant	Exon 5 of 11	5	NM_001003681.3	ENSP00000216106.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	0.0096	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.094	T;.;T
Eigen	Benign	0.0036
Eigen_PC	Benign	-0.041
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.90	.;.;L
PhyloP100		1.6
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-4.7	D;D;N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;D;D
Sift4G	Benign	0.32	T;T;T
Polyphen		0.98	.;.;D
Vest4		0.62
MutPred		0.27		.;.;Gain of relative solvent accessibility (P = 0.0289);
MVP		0.57
MPC		0.20
ClinPred		0.91	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.32
gMVP		0.38
Mutation Taster		=92/8	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: rs760079226; hg19: chr22-35660908;