rs199923448

Variant names:

• chr10-34382893-C-T
• rs199923448
• NM_001184785.2:c.1046G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-34382893-C-T
• chr10-34382893-C-A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001184785.2(PARD3):​c.1046G>A​(p.Arg349His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,613,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: PARD3 NM_001184785.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 O:1
• Conservation: PhyloP100: 7.33
• Publications: 5 publications found

Genes affected

PARD3 (HGNC:16051): (par-3 family cell polarity regulator) This gene encodes a member of the PARD protein family. PARD family members interact with other PARD family members and other proteins; they affect asymmetrical cell division and direct polarized cell growth. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16889134).
• BS2: High AC in GnomAd4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001184785.2. 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
	PARD3	NM_001184785.2	MANE Select	c.1046G>A	p.Arg349His	missense	Exon 9 of 25	NP_001171714.1	Q8TEW0-2
	PARD3	NM_019619.4		c.1046G>A	p.Arg349His	missense	Exon 9 of 25	NP_062565.2
	PARD3	NM_001184786.2		c.1046G>A	p.Arg349His	missense	Exon 9 of 24	NP_001171715.1	Q8TEW0-11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARD3	ENST00000374788.8	TSL:1 MANE Select	c.1046G>A	p.Arg349His	missense	Exon 9 of 25	ENSP00000363920.3	Q8TEW0-2
	PARD3	ENST00000374789.8	TSL:1	c.1046G>A	p.Arg349His	missense	Exon 9 of 25	ENSP00000363921.3	Q8TEW0-1
	PARD3	ENST00000545693.5	TSL:1	c.1046G>A	p.Arg349His	missense	Exon 9 of 24	ENSP00000443147.1	Q8TEW0-11

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152056 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

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: 0.0000557 AC: 14 AN: 251288 AF XY: 0.0000589

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000652

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000124 AC: 181 AN: 1461816 Hom.: 0 Cov.: 32 AF XY: 0.000113 AC XY: 82 AN XY: 727210

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00396 AC: 157 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111976

Other (OTH) AF: 0.0000662 AC: 4 AN: 60392

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74396

African (AFR) AF: 0.0000723 AC: 3 AN: 41514

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000824 Hom.: 0

Bravo AF: 0.0000491

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	-	-	Neural tube defect (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.17	T
MetaSVM	Uncertain	-0.0027	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.3
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.54
Sift	Benign	0.11	T
Sift4G	Benign	0.23	T
Polyphen		0.98	D
Vest4		0.67
MVP		0.76
MPC		0.58
ClinPred		0.35	T
GERP RS		5.7
Varity_R		0.22
gMVP		0.60
Mutation Taster		=61/39	polymorphism

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: rs199923448; hg19: chr10-34671821; COSMIC: COSV60745933;