NM_001006681.2:c.434A>G

Variant names:

• chrX-57120196-T-C
• rs1401098523
• NM_001006681.2:c.434A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001006681.2(SPIN2B):​c.434A>G​(p.Asp145Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000638 in 1,097,682 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0000064 (0 hom. 1 hem.)
• Consequence: SPIN2B NM_001006681.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.53
• Publications: 0 publications found

Genes affected

SPIN2B (HGNC:33147): (spindlin family member 2B) Enables methylated histone binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006681.2. 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
	SPIN2B	NM_001006681.2	MANE Select	c.434A>G	p.Asp145Gly	missense	Exon 2 of 2	NP_001006682.1	Q9BPZ2
	SPIN2B	NM_001006682.2		c.434A>G	p.Asp145Gly	missense	Exon 2 of 2	NP_001006683.1	Q9BPZ2
	SPIN2B	NM_001006683.2		c.434A>G	p.Asp145Gly	missense	Exon 2 of 2	NP_001006684.1	Q9BPZ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIN2B	ENST00000434397.3	TSL:1 MANE Select	c.434A>G	p.Asp145Gly	missense	Exon 2 of 2	ENSP00000404314.2	Q9BPZ2
	SPIN2B	ENST00000275988.5	TSL:1	c.434A>G	p.Asp145Gly	missense	Exon 2 of 2	ENSP00000275988.5	Q9BPZ2
	SPIN2B	ENST00000333933.3	TSL:1	c.434A>G	p.Asp145Gly	missense	Exon 2 of 2	ENSP00000335008.3	Q9BPZ2

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome AF: 0.00000638 AC: 7 AN: 1097682 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363044

African (AFR) AF: 0.00 AC: 0 AN: 26392

American (AMR) AF: 0.00 AC: 0 AN: 35190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.00 AC: 0 AN: 53929

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000832 AC: 7 AN: 841844

Other (OTH) AF: 0.00 AC: 0 AN: 46071

GnomAD4 genome Cov.: 19

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.58
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0072	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L
PhyloP100		6.5
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.18
Sift	Benign	0.059	T
Sift4G	Benign	0.21	T
Polyphen		0.059	B
Vest4		0.42
MutPred		0.41		Gain of MoRF binding (P = 0.0951)
MVP		0.35
MPC		3.3
ClinPred		0.97	D
GERP RS		2.4
PromoterAI		0.034	Neutral
Varity_R		0.82
gMVP		0.80
Mutation Taster		=69/31	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: rs1401098523; hg19: chrX-57146629;