9-4662564-C-G

Variant names:

• chr9-4662564-C-G
• rs747926946
• NM_203453.5:c.189C>G

Variant summary

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

The NM_203453.5(PLPP6):​c.189C>G​(p.Ser63Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLPP6 NM_203453.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42
• Publications: 0 publications found

Genes affected

PLPP6 (HGNC:23682): (phospholipid phosphatase 6) Enables lipid phosphatase activity. Involved in phospholipid dephosphorylation. Predicted to be located in plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPATA6L (HGNC:25472): (spermatogenesis associated 6 like) Predicted to enable myosin light chain binding activity. Predicted to be involved in spermatogenesis. Predicted to be located in sperm connecting piece. [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=0.102175504).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203453.5. 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
	PLPP6	NM_203453.5	MANE Select	c.189C>G	p.Ser63Arg	missense	Exon 1 of 1	NP_982278.3	Q8IY26
	SPATA6L	NM_001353486.2	MANE Select	c.40-528G>C		intron	N/A	NP_001340415.1	Q8N4H0-1
	SPATA6L	NM_001353484.2		c.40-528G>C		intron	N/A	NP_001340413.1	A0AA34QVF8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPP6	ENST00000381883.5	TSL:6 MANE Select	c.189C>G	p.Ser63Arg	missense	Exon 1 of 1	ENSP00000371307.2	Q8IY26
	SPATA6L	ENST00000682582.1	MANE Select	c.40-528G>C		intron	N/A	ENSP00000506787.1	Q8N4H0-1
	SPATA6L	ENST00000451763.6	TSL:1	n.189-528G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.4
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.12
Sift	Benign	0.081	T
Sift4G	Benign	0.084	T
Polyphen		0.14	B
Vest4		0.13
MutPred		0.21		Gain of MoRF binding (P = 0.0066)
MVP		0.068
MPC		1.2
ClinPred		0.84	D
GERP RS		3.0
PromoterAI		0.080	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.19
gMVP		0.65
Mutation Taster		=35/65	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs747926946; hg19: chr9-4662564;