10-122441338-T-C

Variant names:

• chr10-122441338-T-C
• rs6585829
• NM_001377230.1:c.*11400T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021622.5(PLEKHA1):​c.*11400T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.859 in 152,030 control chromosomes in the GnomAD database, including 56,192 homozygotes. 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 0.86 (56176 hom., cov: 29)
  • Exomes 𝑓: 0.86 (16 hom.)
• Consequence: PLEKHA1 NM_021622.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 4 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]

HTRA1-AS1 (HGNC:58122):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021622.5. 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
	PLEKHA1	NM_001377230.1		c.*11400T>C		3_prime_UTR	Exon 13 of 13	NP_001364159.1	Q9HB21-1
	PLEKHA1	NM_001377231.1		c.*11400T>C		3_prime_UTR	Exon 15 of 15	NP_001364160.1	Q9HB21-1
	PLEKHA1	NM_001377232.1		c.*11400T>C		3_prime_UTR	Exon 14 of 14	NP_001364161.1	Q9HB21-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTRA1-AS1	ENST00000650300.1		n.1853-4706A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.859 AC: 130398 AN: 151870 Hom.: 56119 Cov.: 29

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.941

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.844

GnomAD4 exome AF: 0.857 AC: 36 AN: 42 Hom.: 16 Cov.: 0 AF XY: 0.933 AC XY: 28 AN XY: 30

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.824 AC: 28 AN: 34

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.859 AC: 130512 AN: 151988 Hom.: 56176 Cov.: 29 AF XY: 0.864 AC XY: 64221 AN XY: 74318

African (AFR) AF: 0.877 AC: 36320 AN: 41408

American (AMR) AF: 0.880 AC: 13438 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2659 AN: 3468

East Asian (EAS) AF: 0.941 AC: 4840 AN: 5144

South Asian (SAS) AF: 0.852 AC: 4102 AN: 4816

European-Finnish (FIN) AF: 0.917 AC: 9712 AN: 10588

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.833 AC: 56633 AN: 67976

Other (OTH) AF: 0.846 AC: 1789 AN: 2114

Alfa AF: 0.837 Hom.: 14610

Bravo AF: 0.856

Asia WGS AF: 0.912 AC: 3172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.83
DANN	Benign	0.26
PhyloP100		-1.7

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: rs6585829; hg19: chr10-124200854;