X-143509162-T-G

Variant names:

• chrX-143509162-T-G
• NM_001009609.4:c.79A>C
• SPANXN3 p.Met27Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001009609.4(SPANXN3):​c.79A>C​(p.Met27Leu) variant causes a missense, splice region 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. 16/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: SPANXN3 NM_001009609.4 missense, splice_region
• Scores: Splicing: ADA: 0.0002483
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286
• Publications: 0 publications found

Genes affected

SPANXN3 (HGNC:33176): (SPANX family member N3)

ENSG00000227303 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2728619).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009609.4. 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
	SPANXN3	NM_001009609.4	MANE Select	c.79A>C	p.Met27Leu	missense splice_region	Exon 2 of 2	NP_001009609.2	Q5MJ09

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPANXN3	ENST00000370503.2	TSL:1 MANE Select	c.79A>C	p.Met27Leu	missense splice_region	Exon 2 of 2	ENSP00000359534.2	Q5MJ09
	ENSG00000227303	ENST00000431432.1	TSL:3	n.269-447T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.49
FATHMM_MKL	Benign	0.027	N
M_CAP	Benign	0.00090	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.29
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.10
Sift	Benign	0.16	T
Sift4G	Benign	0.36	T
gMVP		0.0054
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00025
dbscSNV1_RF	Benign	0.024
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-142596991;