chr12-19130072-C-T

Variant names:

• chr12-19130072-C-T
• rs567317913
• NM_001256470.2:c.111C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6 BP7

The NM_001256470.2(PLEKHA5):​c.111C>T​(p.Thr37Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000716 in 1,591,418 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000074 (1 hom.)
• Consequence: PLEKHA5 NM_001256470.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.01
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 12-19130072-C-T is Benign according to our data. Variant chr12-19130072-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3054146.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.01 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256470.2. 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
	PLEKHA5	NM_001256470.2	MANE Select	c.111C>T	p.Thr37Thr	synonymous	Exon 2 of 32	NP_001243399.1	Q9HAU0-6
	PLEKHA5	NM_001385923.1		c.111C>T	p.Thr37Thr	synonymous	Exon 2 of 31	NP_001372852.1
	PLEKHA5	NM_001385924.1		c.111C>T	p.Thr37Thr	synonymous	Exon 2 of 31	NP_001372853.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA5	ENST00000429027.7	TSL:1 MANE Select	c.111C>T	p.Thr37Thr	synonymous	Exon 2 of 32	ENSP00000404296.2	Q9HAU0-6
	PLEKHA5	ENST00000538714.5	TSL:1	c.111C>T	p.Thr37Thr	synonymous	Exon 2 of 28	ENSP00000439673.1	Q9HAU0-2
	PLEKHA5	ENST00000299275.10	TSL:1	c.111C>T	p.Thr37Thr	synonymous	Exon 2 of 26	ENSP00000299275.6	Q9HAU0-1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152062 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000114 AC: 24 AN: 210322 AF XY: 0.000139

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000743 AC: 107 AN: 1439248 Hom.: 1 Cov.: 31 AF XY: 0.0000994 AC XY: 71 AN XY: 714470

African (AFR) AF: 0.00 AC: 0 AN: 32074

American (AMR) AF: 0.00 AC: 0 AN: 42452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25438

East Asian (EAS) AF: 0.00 AC: 0 AN: 38006

South Asian (SAS) AF: 0.00116 AC: 96 AN: 82598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00000363 AC: 4 AN: 1102352

Other (OTH) AF: 0.000118 AC: 7 AN: 59490

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152170 Hom.: 0 Cov.: 30 AF XY: 0.0000807 AC XY: 6 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41556

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5098

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PLEKHA5-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Uncertain	0.98
PhyloP100		2.0
PromoterAI		0.085	Neutral
Mutation Taster		=79/21	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: rs567317913; hg19: chr12-19283006;