rs1313249917

Variant names:

• chr19-14053943-G-C
• rs1313249917
• NM_001145028.2:c.1729C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-14053943-G-C
• chr19-14053943-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145028.2(PALM3):​c.1729C>G​(p.Leu577Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: PALM3 NM_001145028.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195

Genes affected

PALM3 (HGNC:33274): (paralemmin 3) Predicted to enable ATP binding activity. Involved in Toll signaling pathway; negative regulation of cytokine-mediated signaling pathway; and response to lipopolysaccharide. Predicted to be located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06255317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALM3	NM_001145028.2	c.1729C>G	p.Leu577Val	missense_variant	Exon 7 of 7	ENST00000669674.2	NP_001138500.2
PALM3	NM_001367327.1	c.1531C>G	p.Leu511Val	missense_variant	Exon 5 of 5		NP_001354256.1
PALM3	XM_047438763.1	c.1648C>G	p.Leu550Val	missense_variant	Exon 6 of 6		XP_047294719.1
PALM3	XM_047438764.1	c.1531C>G	p.Leu511Val	missense_variant	Exon 5 of 5		XP_047294720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALM3	ENST00000669674.2	c.1729C>G	p.Leu577Val	missense_variant	Exon 7 of 7		NM_001145028.2	ENSP00000499271.1
PALM3	ENST00000340790.9	c.1684C>G	p.Leu562Val	missense_variant	Exon 6 of 6	5		ENSP00000344996.3
PALM3	ENST00000661591.1	c.1609C>G	p.Leu537Val	missense_variant	Exon 4 of 4			ENSP00000499248.1
PALM3	ENST00000589048.2	c.1531C>G	p.Leu511Val	missense_variant	Exon 5 of 5	3		ENSP00000465701.2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152082 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152082 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74294

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.40
DANN	Benign	0.94
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.010
Sift	Benign	0.17	T
Sift4G	Benign	1.0	T
Polyphen		0.035	B
Vest4		0.035
MutPred		0.18		Gain of sheet (P = 0.0477);
MVP		0.014
ClinPred		0.075	T
GERP RS		-0.61
Varity_R		0.044
gMVP		0.032

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

Publications

LitVar

Other links and lift over

dbSNP: rs1313249917; hg19: chr19-14164755;