10-34111506-G-C

Variant names:

• chr10-34111506-G-C
• rs371401357
• NM_001184785.2:c.3725C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001184785.2(PARD3):​c.3725C>G​(p.Ser1242Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. S1242Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PARD3 NM_001184785.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.36
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13943323).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARD3	NM_001184785.2	c.3725C>G	p.Ser1242Cys	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.3725C>G	p.Ser1242Cys	missense_variant	Exon 25 of 25	1	NM_001184785.2	ENSP00000363920.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.14	.;.;T;.;.;.;.;.
Eigen	Benign	0.094
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D;D
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;.;N;.;.;.;.;.
PhyloP100		6.4
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N;N;N
REVEL	Benign	0.095
Sift	Benign	0.069	T;T;T;T;T;T;T;T
Sift4G	Uncertain	0.038	D;D;D;D;D;D;D;D
Polyphen		0.25	B;.;B;B;B;B;B;.
Vest4		0.25
MutPred		0.24		.;.;Gain of catalytic residue at S1245 (P = 0.0297);.;.;.;.;.;
MVP		0.25
MPC		0.18
ClinPred		0.48	T
GERP RS		5.9
Varity_R		0.10
gMVP		0.25
Mutation Taster		=91/9	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: rs371401357; hg19: chr10-34400434;