rs4405249

Variant names:

• chr10-122424216-T-A
• rs4405249
• NM_001001974.4:c.699T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-122424216-T-A
• chr10-122424216-T-C
• chr10-122424216-T-G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001001974.4(PLEKHA1):​c.699T>A​(p.Arg233Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.0 (0 hom., cov: 19)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLEKHA1 NM_001001974.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 31 publications found

Genes affected

PLEKHA1 (HGNC:14335): (pleckstrin homology domain containing A1) This gene encodes a pleckstrin homology domain-containing adapter protein. The encoded protein is localized to the plasma membrane where it specifically binds phosphatidylinositol 3,4-bisphosphate. This protein may be involved in the formation of signaling complexes in the plasma membrane. Polymorphisms in this gene are associated with age-related macular degeneration. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 5.[provided by RefSeq, Sep 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-1.57 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA1	NM_001001974.4	c.699T>A	p.Arg233Arg	synonymous_variant	Exon 9 of 12	ENST00000368990.8	NP_001001974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA1	ENST00000368990.8	c.699T>A	p.Arg233Arg	synonymous_variant	Exon 9 of 12	1	NM_001001974.4	ENSP00000357986.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 143846 Hom.: 0 Cov.: 19

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 221372 AF XY: 0.00

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 Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1432446 Hom.: 0 Cov.: 42 AF XY: 0.00 AC XY: 0 AN XY: 712326

African (AFR) AF: 0.00 AC: 0 AN: 31244

American (AMR) AF: 0.00 AC: 0 AN: 36006

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25280

East Asian (EAS) AF: 0.00 AC: 0 AN: 39436

South Asian (SAS) AF: 0.00 AC: 0 AN: 79770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5052

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103780

Other (OTH) AF: 0.00 AC: 0 AN: 59048

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 143846 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 69274

African (AFR) AF: 0.00 AC: 0 AN: 38884

American (AMR) AF: 0.00 AC: 0 AN: 14134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3428

East Asian (EAS) AF: 0.00 AC: 0 AN: 4956

South Asian (SAS) AF: 0.00 AC: 0 AN: 4438

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66628

Other (OTH) AF: 0.00 AC: 0 AN: 1962

Alfa AF: 0.00 Hom.: 105616

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.35
DANN	Benign	0.53
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs4405249; hg19: chr10-124183732;