rs33911350

Variant names:

• chr1-204273710-A-C
• rs33911350
• NM_014935.5:c.18T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-204273710-A-C
• chr1-204273710-A-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_014935.5(PLEKHA6):​c.18T>G​(p.Gly6Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,612,072 control chromosomes in the GnomAD database, including 26,090 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 0.18 (2522 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23568 hom.)
• Consequence: PLEKHA6 NM_014935.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260
• Publications: 15 publications found

Genes affected

PLEKHA6 (HGNC:17053): (pleckstrin homology domain containing A6)

PLEKHA6 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=0.26 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014935.5. 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
	PLEKHA6	NM_014935.5	MANE Select	c.18T>G	p.Gly6Gly	synonymous	Exon 3 of 23	NP_055750.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA6	ENST00000272203.8	TSL:1 MANE Select	c.18T>G	p.Gly6Gly	synonymous	Exon 3 of 23	ENSP00000272203.2
	PLEKHA6	ENST00000637508.1	TSL:5	c.18T>G	p.Gly6Gly	synonymous	Exon 3 of 27	ENSP00000490182.1
	PLEKHA6	ENST00000943171.1		c.18T>G	p.Gly6Gly	synonymous	Exon 3 of 26	ENSP00000613230.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27062 AN: 151726 Hom.: 2520 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.170

GnomAD2 exomes AF: 0.193 AC: 48375 AN: 251220 AF XY: 0.190

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.243

Gnomad ASJ exome AF: 0.136

Gnomad EAS exome AF: 0.274

Gnomad FIN exome AF: 0.245

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.176 AC: 256808 AN: 1460228 Hom.: 23568 Cov.: 31 AF XY: 0.176 AC XY: 127830 AN XY: 726526

African (AFR) AF: 0.133 AC: 4454 AN: 33460

American (AMR) AF: 0.238 AC: 10622 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 3626 AN: 26122

East Asian (EAS) AF: 0.259 AC: 10291 AN: 39684

South Asian (SAS) AF: 0.182 AC: 15733 AN: 86228

European-Finnish (FIN) AF: 0.241 AC: 12893 AN: 53404

Middle Eastern (MID) AF: 0.138 AC: 798 AN: 5766

European-Non Finnish (NFE) AF: 0.169 AC: 187581 AN: 1110506

Other (OTH) AF: 0.179 AC: 10810 AN: 60340

GnomAD4 genome AF: 0.178 AC: 27079 AN: 151844 Hom.: 2522 Cov.: 32 AF XY: 0.184 AC XY: 13659 AN XY: 74200

African (AFR) AF: 0.141 AC: 5856 AN: 41392

American (AMR) AF: 0.212 AC: 3242 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 490 AN: 3468

East Asian (EAS) AF: 0.283 AC: 1453 AN: 5138

South Asian (SAS) AF: 0.197 AC: 949 AN: 4810

European-Finnish (FIN) AF: 0.251 AC: 2647 AN: 10534

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11946 AN: 67924

Other (OTH) AF: 0.170 AC: 357 AN: 2098

Alfa AF: 0.168 Hom.: 2531

Bravo AF: 0.172

Asia WGS AF: 0.273 AC: 950 AN: 3478

EpiCase AF: 0.165

EpiControl AF: 0.166

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs33911350; hg19: chr1-204242838; COSMIC: COSV55331667; COSMIC: COSV55331667;