chr2-27581943-C-G

Variant names:

• chr2-27581943-C-G
• rs1286741422
• NM_032266.5:c.15583C>G

Variant summary

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

The NM_032266.5(SPATA31H1):​c.15583C>G​(p.His5195Asp) 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. 15/21 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. H5195Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPATA31H1 NM_032266.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• Publications: 0 publications found

Genes affected

SPATA31H1 (HGNC:25275): (SPATA31 subfamily H member 1) Located in extracellular exosome and nucleus. [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=0.11249238).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032266.5. 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
	SPATA31H1	NM_032266.5	MANE Select	c.15583C>G	p.His5195Asp	missense	Exon 5 of 5	NP_115642.4	C9JG08

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31H1	ENST00000447166.3	TSL:3 MANE Select	c.15583C>G	p.His5195Asp	missense	Exon 5 of 5	ENSP00000403181.2	C9JG08

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.4
DANN	Benign	0.54
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.15
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.070
Sift	Benign	0.29	T
Sift4G	Benign	0.18	T
Polyphen		0.94	P
Vest4		0.13
MutPred		0.24		Loss of glycosylation at P1793 (P = 0.106)
MVP		0.072
MPC		0.12
ClinPred		0.25	T
GERP RS		-0.032
Varity_R		0.056
gMVP		0.031
Mutation Taster		=98/2	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: rs1286741422; hg19: chr2-27804810;