X-57120196-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPIN2B	NM_001006681.2	c.434A>G	p.Asp145Gly	missense_variant	Exon 2 of 2	ENST00000434397.3	NP_001006682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPIN2B	ENST00000434397.3	c.434A>G	p.Asp145Gly	missense_variant	Exon 2 of 2	1	NM_001006681.2	ENSP00000404314.2

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000832

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 19

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.434A>G (p.D145G) alteration is located in exon 2 (coding exon 1) of the SPIN2B gene. This alteration results from a A to G substitution at nucleotide position 434, causing the aspartic acid (D) at amino acid position 145 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	.;T;T
M_CAP	Benign	0.0072	T
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L;L;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-4.3	D;D;D
REVEL	Benign	0.18
Sift	Benign	0.059	T;T;T
Sift4G	Benign	0.21	T;T;.
Polyphen		0.059	B;B;.
Vest4		0.42
MutPred		0.41		Gain of MoRF binding (P = 0.0951);Gain of MoRF binding (P = 0.0951);Gain of MoRF binding (P = 0.0951);
MVP		0.35
MPC		3.3
ClinPred		0.97	D
GERP RS		2.4
Varity_R		0.82
gMVP		0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs1401098523; hg19: chrX-57146629;