rs139525088

Variant names:

• chr12-19129829-C-G
• rs139525088
• NM_001256470.2:c.30C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-19129829-C-G
• chr12-19129829-C-T

Variant summary

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

The NM_001256470.2(PLEKHA5):​c.30C>G​(p.Ile10Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I10I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PLEKHA5 NM_001256470.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 0 publications found

Genes affected

PLEKHA5 (HGNC:30036): (pleckstrin homology domain containing A5) Predicted to enable phosphatidylinositol phosphate binding activity. Predicted to act upstream of or within reproductive system development. Located 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=0.09234473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA5	NM_001256470.2	c.30C>G	p.Ile10Met	missense_variant	Exon 1 of 32	ENST00000429027.7	NP_001243399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA5	ENST00000429027.7	c.30C>G	p.Ile10Met	missense_variant	Exon 1 of 32	1	NM_001256470.2	ENSP00000404296.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452974 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722986

African (AFR) AF: 0.00 AC: 0 AN: 32450

American (AMR) AF: 0.00 AC: 0 AN: 44140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25834

East Asian (EAS) AF: 0.00 AC: 0 AN: 38720

South Asian (SAS) AF: 0.00 AC: 0 AN: 85484

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108284

Other (OTH) AF: 0.00 AC: 0 AN: 59958

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.0088	.;.;T;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.51	T;T;T;T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.092	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L;L;L
PhyloP100		0.21
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.32	N;N;N;N
REVEL	Benign	0.071
Sift	Benign	0.19	T;T;D;T
Sift4G	Benign	0.27	T;T;T;T
Polyphen		0.72, 0.81	.;.;P;P
Vest4		0.22
MutPred		0.51		Gain of catalytic residue at L7 (P = 0);Gain of catalytic residue at L7 (P = 0);Gain of catalytic residue at L7 (P = 0);Gain of catalytic residue at L7 (P = 0);
MVP		0.093
MPC		1.0
ClinPred		0.18	T
GERP RS		2.5
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.51
Mutation Taster		=90/10	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: rs139525088; hg19: chr12-19282763;