NM_001006681.2:c.639T>A

Variant names:

• chrX-57119991-A-T
• rs764588115
• NM_001006681.2:c.639T>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001006681.2(SPIN2B):​c.639T>A​(p.His213Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,207,519 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000091 (0 hom., 1 hem., cov: 20)
  • Exomes 𝑓: 0.000020 (0 hom. 9 hem.)
• Consequence: SPIN2B NM_001006681.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.041706264).
• BS2: High Hemizygotes in GnomAdExome4 at 9 gene

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.639T>A	p.His213Gln	missense	Exon 2 of 2	NP_001006682.1	Q9BPZ2
	SPIN2B	NM_001006682.2		c.639T>A	p.His213Gln	missense	Exon 2 of 2	NP_001006683.1	Q9BPZ2
	SPIN2B	NM_001006683.2		c.639T>A	p.His213Gln	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.639T>A	p.His213Gln	missense	Exon 2 of 2	ENSP00000404314.2	Q9BPZ2
	SPIN2B	ENST00000275988.5	TSL:1	c.639T>A	p.His213Gln	missense	Exon 2 of 2	ENSP00000275988.5	Q9BPZ2
	SPIN2B	ENST00000333933.3	TSL:1	c.639T>A	p.His213Gln	missense	Exon 2 of 2	ENSP00000335008.3	Q9BPZ2

Frequencies

GnomAD3 genomes AF: 0.00000915 AC: 1 AN: 109298 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000292

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000550 AC: 10 AN: 181832 AF XY: 0.0000753

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000724

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000200 AC: 22 AN: 1098169 Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 9 AN XY: 363523

African (AFR) AF: 0.00 AC: 0 AN: 26402

American (AMR) AF: 0.00 AC: 0 AN: 35196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.000530 AC: 16 AN: 30206

South Asian (SAS) AF: 0.0000370 AC: 2 AN: 54095

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00000237 AC: 2 AN: 842120

Other (OTH) AF: 0.0000434 AC: 2 AN: 46095

GnomAD4 genome AF: 0.00000914 AC: 1 AN: 109350 Hom.: 0 Cov.: 20 AF XY: 0.0000316 AC XY: 1 AN XY: 31642

African (AFR) AF: 0.00 AC: 0 AN: 30005

American (AMR) AF: 0.00 AC: 0 AN: 10274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2615

East Asian (EAS) AF: 0.000293 AC: 1 AN: 3414

South Asian (SAS) AF: 0.00 AC: 0 AN: 2448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52471

Other (OTH) AF: 0.00 AC: 0 AN: 1481

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000494 AC: 6

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	Uncertain	0.39
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	17
DANN	Benign	0.73
DEOGEN2	Benign	0.0091	T
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		1.0
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	0.43	N
REVEL	Benign	0.17
Sift	Benign	0.53	T
Sift4G	Benign	0.34	T
Polyphen		0.91	P
Vest4		0.17
MutPred		0.34		Gain of catalytic residue at H213 (P = 0.0678)
MVP		0.46
MPC		1.8
ClinPred		0.12	T
GERP RS		1.4
Varity_R		0.17
gMVP		0.24
Mutation Taster		=97/3	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: rs764588115; hg19: chrX-57146424;