chr1-99688927-A-G

Variant names:

• chr1-99688927-A-G
• NM_017734.5:c.667A>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 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
• Publications: 0 publications found

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

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=0.08772996).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017734.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALMD	NM_017734.5	MANE Select	c.667A>G	p.Asn223Asp	missense	Exon 7 of 8	NP_060204.1	Q9NP74-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALMD	ENST00000263174.9	TSL:1 MANE Select	c.667A>G	p.Asn223Asp	missense	Exon 7 of 8	ENSP00000263174.4	Q9NP74-1
	PALMD	ENST00000605497.5	TSL:1	c.667A>G	p.Asn223Asp	missense	Exon 7 of 7	ENSP00000473839.1	S4R313
	PALMD	ENST00000496843.1	TSL:1	n.3826A>G		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.93	L
PhyloP100		2.2
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.016
Sift	Benign	0.18	T
Sift4G	Benign	0.62	T
Polyphen		0.026	B
Vest4		0.12
MutPred		0.33		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
Mutation Taster		=99/1	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

hg19: chr1-100154483;