rs144844232

Variant names:

• chr10-34111475-C-G
• rs144844232
• NM_001184785.2:c.3756G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-34111475-C-G
• chr10-34111475-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS2

The NM_001184785.2(PARD3):​c.3756G>C​(p.Glu1252Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1252G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: PARD3 NM_001184785.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.558
• Publications: 1 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046348363).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARD3	NM_001184785.2	c.3756G>C	p.Glu1252Asp	missense_variant	Exon 25 of 25	ENST00000374788.8	NP_001171714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARD3	ENST00000374788.8	c.3756G>C	p.Glu1252Asp	missense_variant	Exon 25 of 25	1	NM_001184785.2	ENSP00000363920.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251454 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727234

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	.;.;T;.;.;.;.;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.85	D;D;D;D;D;D;D;D
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.046	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.11	.;.;N;.;.;.;.;.
PhyloP100		0.56
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.82	N;N;N;N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.26	T;T;T;T;T;T;T;T
Sift4G	Benign	0.52	T;T;T;T;T;T;T;T
Polyphen		0.0050	B;.;B;B;B;B;B;.
Vest4		0.10
MutPred		0.16		.;.;Loss of helix (P = 0.0304);.;.;.;.;.;
MVP		0.29
MPC		0.077
ClinPred		0.23	T
GERP RS		3.0
Varity_R		0.077
gMVP		0.11
Mutation Taster		=84/16	polymorphism

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: rs144844232; hg19: chr10-34400403;