1-99689117-G-A

Position:

• chr1-99689117-G-A

Variant summary

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

The NM_017734.5(PALMD):​c.857G>A​(p.Arg286Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PALMD NM_017734.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.732

Genes affected

PALMD (HGNC:15846): (palmdelphin) Predicted to be involved in regulation of cell shape. Predicted to be located in dendrite. Predicted to be active in cytoplasm. [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=0.058310777).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALMD	NM_017734.5	c.857G>A	p.Arg286Lys	missense_variant	7/8	ENST00000263174.9	NP_060204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALMD	ENST00000263174.9	c.857G>A	p.Arg286Lys	missense_variant	7/8	1	NM_017734.5	ENSP00000263174	P1
PALMD	ENST00000605497.5	c.857G>A	p.Arg286Lys	missense_variant	7/7	1		ENSP00000473839
PALMD	ENST00000496843.1	n.4016G>A		non_coding_transcript_exon_variant	4/5	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2023

The c.857G>A (p.R286K) alteration is located in exon 7 (coding exon 7) of the PALMD gene. This alteration results from a G to A substitution at nucleotide position 857, causing the arginine (R) at amino acid position 286 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.014	T;.;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.64	T;T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.058	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.6	L;.;.
MutationTaster	Benign	0.99	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.20	N;.;.
REVEL	Benign	0.031
Sift	Benign	0.37	T;.;.
Sift4G	Benign	0.63	T;T;T
Polyphen		0.0020	B;.;B
Vest4		0.12
MutPred		0.34		Gain of methylation at R286 (P = 0.0148);Gain of methylation at R286 (P = 0.0148);.;
MVP		0.28
MPC		0.034
ClinPred		0.051	T
GERP RS		2.9
Varity_R		0.079
gMVP		0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-100154673;