9-4662564-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_203453.5(PLPP6):​c.189C>T​(p.Ser63Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,433,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PLPP6 NM_203453.5 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=2.42 with no splicing effect.

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>T	p.Ser63Ser	synonymous	Exon 1 of 1	NP_982278.3	Q8IY26
	SPATA6L	NM_001353486.2	MANE Select	c.40-528G>A		intron	N/A	NP_001340415.1	Q8N4H0-1
	SPATA6L	NM_001353484.2		c.40-528G>A		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>T	p.Ser63Ser	synonymous	Exon 1 of 1	ENSP00000371307.2	Q8IY26
	SPATA6L	ENST00000682582.1	MANE Select	c.40-528G>A		intron	N/A	ENSP00000506787.1	Q8N4H0-1
	SPATA6L	ENST00000451763.6	TSL:1	n.189-528G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000948 AC: 2 AN: 210908 AF XY: 0.0000170

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000308

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000104

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1433076 Hom.: 0 Cov.: 33 AF XY: 0.00000281 AC XY: 2 AN XY: 712568

African (AFR) AF: 0.00 AC: 0 AN: 32892

American (AMR) AF: 0.0000233 AC: 1 AN: 42942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25326

East Asian (EAS) AF: 0.00 AC: 0 AN: 39432

South Asian (SAS) AF: 0.00 AC: 0 AN: 84346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4390

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106356

Other (OTH) AF: 0.00 AC: 0 AN: 59394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.5
DANN	Benign	0.96
PhyloP100		2.4
PromoterAI		-0.065	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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;