1-99688927-A-G

Position:

• chr1-99688927-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017734.5(PALMD):​c.667A>G​(p.Asn223Asp) 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: 2.18

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08772996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALMD	NM_017734.5	c.667A>G	p.Asn223Asp	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.667A>G	p.Asn223Asp	missense_variant	7/8	1	NM_017734.5	ENSP00000263174	P1
PALMD	ENST00000605497.5	c.667A>G	p.Asn223Asp	missense_variant	7/7	1		ENSP00000473839
PALMD	ENST00000496843.1	n.3826A>G		non_coding_transcript_exon_variant	4/5	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

May 20, 2024

The c.667A>G (p.N223D) alteration is located in exon 7 (coding exon 7) of the PALMD gene. This alteration results from a A to G substitution at nucleotide position 667, causing the asparagine (N) at amino acid position 223 to be replaced by an aspartic acid (D). 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	0.070
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.92
DEOGEN2	Benign	0.0028	T;.;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.088	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.93	L;.;.
MutationTaster	Benign	0.99	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.70	N;.;.
REVEL	Benign	0.016
Sift	Benign	0.18	T;.;.
Sift4G	Benign	0.62	T;T;T
Polyphen		0.026	B;.;B
Vest4		0.12
MutPred		0.33		Gain of phosphorylation at S221 (P = 0.1169);Gain of phosphorylation at S221 (P = 0.1169);.;
MVP		0.38
MPC		0.036
ClinPred		0.12	T
GERP RS		2.0
Varity_R		0.070
gMVP		0.13

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: chr1-100154483;