NM_014935.5:c.-95+39042A>C

Variant names:

• chr1-204320652-T-G
• rs17333933
• NM_014935.5:c.-95+39042A>C

Variant summary

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

The NM_014935.5(PLEKHA6):​c.-95+39042A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 160,772 control chromosomes in the GnomAD database, including 7,838 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 0.31 (7337 hom., cov: 32)
  • Exomes 𝑓: 0.33 (501 hom.)
• Consequence: PLEKHA6 NM_014935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA6	NM_014935.5	c.-95+39042A>C		intron_variant	Intron 1 of 22	ENST00000272203.8	NP_055750.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA6	ENST00000272203.8	c.-95+39042A>C		intron_variant	Intron 1 of 22	1	NM_014935.5	ENSP00000272203.2

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46430 AN: 151966 Hom.: 7317 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.326 AC: 2837 AN: 8690 Hom.: 501 AF XY: 0.321 AC XY: 1379 AN XY: 4300

African (AFR) AF: 0.451 AC: 73 AN: 162

American (AMR) AF: 0.0833 AC: 1 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 19 AN: 68

East Asian (EAS) AF: 0.0667 AC: 2 AN: 30

South Asian (SAS) AF: 0.372 AC: 58 AN: 156

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.250 AC: 4 AN: 16

European-Non Finnish (NFE) AF: 0.324 AC: 2588 AN: 7976

Other (OTH) AF: 0.341 AC: 92 AN: 270

GnomAD4 genome AF: 0.306 AC: 46481 AN: 152082 Hom.: 7337 Cov.: 32 AF XY: 0.306 AC XY: 22731 AN XY: 74326

African (AFR) AF: 0.385 AC: 15956 AN: 41476

American (AMR) AF: 0.249 AC: 3806 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 925 AN: 3470

East Asian (EAS) AF: 0.139 AC: 721 AN: 5174

South Asian (SAS) AF: 0.318 AC: 1533 AN: 4818

European-Finnish (FIN) AF: 0.299 AC: 3165 AN: 10584

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19443 AN: 67958

Other (OTH) AF: 0.298 AC: 630 AN: 2112

Alfa AF: 0.291 Hom.: 19943

Bravo AF: 0.300

Asia WGS AF: 0.247 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.19
DANN	Benign	0.72
PhyloP100		-1.4
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: rs17333933; hg19: chr1-204289780;