chrX-56994868-A-T

Variant names:

• chrX-56994868-A-T
• rs762760057
• NM_001010862.3:c.80T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001010862.3(SPIN3):​c.80T>A​(p.Met27Lys) 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. 14/21 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. M27R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: SPIN3 NM_001010862.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 0 publications found

Genes affected

SPIN3 (HGNC:27272): (spindlin family member 3) Enables methylated histone binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be integral component of membrane. Predicted to be active in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.17407379).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010862.3. 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
	SPIN3	NM_001010862.3	MANE Select	c.80T>A	p.Met27Lys	missense	Exon 2 of 2	NP_001010862.2	Q5JUX0-1
	SPIN3	NR_027139.2		n.408T>A		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIN3	ENST00000374919.6	TSL:1 MANE Select	c.80T>A	p.Met27Lys	missense	Exon 2 of 2	ENSP00000364054.3	Q5JUX0-1
	SPIN3	ENST00000478405.1	TSL:1	n.80T>A		non_coding_transcript_exon	Exon 2 of 5	ENSP00000433337.1	Q5JUX0-2
	SPIN3	ENST00000639257.1	TSL:3	n.80T>A		non_coding_transcript_exon	Exon 2 of 5	ENSP00000492259.1	Q5JUX0-2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000552 AC: 1 AN: 181229 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000736

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.096	T
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.3
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.050
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.17	T
Polyphen		0.028	B
Vest4		0.24
MutPred		0.38		Loss of catalytic residue at V23 (P = 0.0337)
MVP		0.14
MPC		0.74
ClinPred		0.16	T
GERP RS		2.5
Varity_R		0.71
gMVP		0.76
Mutation Taster		=89/11	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: rs762760057; hg19: chrX-57021301;