chr22-35265211-G-C

Variant names:

• chr22-35265211-G-C
• rs760999697
• NM_001003681.3:c.823G>C

Variant summary

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

The NM_001003681.3(HMGXB4):​c.823G>C​(p.Ala275Pro) 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. 16/22 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. A275T) 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: 0.562
• Publications: 1 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: 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 (MetaRNN=0.027930021).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGXB4	NM_001003681.3	c.823G>C	p.Ala275Pro	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.823G>C	p.Ala275Pro	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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Benign	0.34
DEOGEN2	Benign	0.0076	T;.;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.57	T;T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.028	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.6	.;.;N
PhyloP100		0.56
PrimateAI	Benign	0.40	T
PROVEAN	Benign	1.2	N;N;N
REVEL	Benign	0.019
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.087
MutPred		0.23		.;.;Gain of loop (P = 3e-04);
MVP		0.25
MPC		0.13
ClinPred		0.047	T
GERP RS		2.3
Varity_R		0.033
gMVP		0.11
Mutation Taster		=96/4	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: rs760999697; hg19: chr22-35661204;