NM_014431.3:c.186-6C>A

Variant names:

• chr10-70529223-C-A
• rs200131551
• NM_014431.3:c.186-6C>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_014431.3(PALD1):​c.186-6C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (873 hom., cov: 13)
  • Exomes 𝑓: 0.054 (2519 hom.)
  • Failed GnomAD Quality Control
• Consequence: PALD1 NM_014431.3 splice_region, intron
• Scores: Splicing: ADA: 0.001613
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0280
• Publications: 1 publications found

Genes affected

PALD1 (HGNC:23530): (phosphatase domain containing paladin 1) Predicted to enable protein tyrosine phosphatase activity. Predicted to be involved in peptidyl-tyrosine dephosphorylation. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 10-70529223-C-A is Benign according to our data. Variant chr10-70529223-C-A is described in ClinVar as Benign. ClinVar VariationId is 768371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014431.3. 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
	PALD1	NM_014431.3	MANE Select	c.186-6C>A		splice_region intron	N/A	NP_055246.2	Q9ULE6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALD1	ENST00000263563.7	TSL:1 MANE Select	c.186-6C>A		splice_region intron	N/A	ENSP00000263563.5	Q9ULE6
	PALD1	ENST00000697571.1		c.186-6C>A		splice_region intron	N/A	ENSP00000513342.1	A0A8V8TMP9
	PALD1	ENST00000893833.1		c.186-6C>A		splice_region intron	N/A	ENSP00000563892.1

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 4894 AN: 69568 Hom.: 871 Cov.: 13

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0344

Gnomad ASJ AF: 0.0820

Gnomad EAS AF: 0.00697

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.00332

Gnomad MID AF: 0.0427

Gnomad NFE AF: 0.0232

Gnomad OTH AF: 0.0723

GnomAD2 exomes AF: 0.0573 AC: 4425 AN: 77240 AF XY: 0.0558

Gnomad AFR exome AF: 0.262

Gnomad AMR exome AF: 0.0297

Gnomad ASJ exome AF: 0.0589

Gnomad EAS exome AF: 0.0101

Gnomad FIN exome AF: 0.0247

Gnomad NFE exome AF: 0.0306

Gnomad OTH exome AF: 0.0475

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0538 AC: 14454 AN: 268840 Hom.: 2519 Cov.: 7 AF XY: 0.0520 AC XY: 7824 AN XY: 150328

African (AFR) AF: 0.261 AC: 2475 AN: 9500

American (AMR) AF: 0.0369 AC: 607 AN: 16440

Ashkenazi Jewish (ASJ) AF: 0.0757 AC: 573 AN: 7566

East Asian (EAS) AF: 0.0305 AC: 300 AN: 9846

South Asian (SAS) AF: 0.0728 AC: 2883 AN: 39602

European-Finnish (FIN) AF: 0.0194 AC: 256 AN: 13182

Middle Eastern (MID) AF: 0.0518 AC: 94 AN: 1814

European-Non Finnish (NFE) AF: 0.0398 AC: 6302 AN: 158146

Other (OTH) AF: 0.0756 AC: 964 AN: 12744

GnomAD4 genome AF: 0.0705 AC: 4910 AN: 69658 Hom.: 873 Cov.: 13 AF XY: 0.0669 AC XY: 2354 AN XY: 35196

African (AFR) AF: 0.186 AC: 3570 AN: 19162

American (AMR) AF: 0.0343 AC: 293 AN: 8550

Ashkenazi Jewish (ASJ) AF: 0.0820 AC: 119 AN: 1452

East Asian (EAS) AF: 0.00736 AC: 19 AN: 2582

South Asian (SAS) AF: 0.108 AC: 162 AN: 1494

European-Finnish (FIN) AF: 0.00332 AC: 23 AN: 6934

Middle Eastern (MID) AF: 0.0374 AC: 8 AN: 214

European-Non Finnish (NFE) AF: 0.0232 AC: 647 AN: 27920

Other (OTH) AF: 0.0711 AC: 69 AN: 970

Alfa AF: 0.0136 Hom.: 37

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	1.5
DANN	Benign	0.86
PhyloP100		0.028
Mutation Taster		=93/7	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0016
dbscSNV1_RF	Benign	0.032
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: rs200131551; hg19: chr10-72288979; COSMIC: COSV54978617;