1-99689038-C-G

Variant names:

• chr1-99689038-C-G
• rs144420060
• NM_017734.5:c.778C>G

Variant summary

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

The NM_017734.5(PALMD):​c.778C>G​(p.Pro260Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,610 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P260S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PALMD NM_017734.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.93
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.778C>G	p.Pro260Ala	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.778C>G	p.Pro260Ala	missense	Exon 7 of 8	ENSP00000263174.4	Q9NP74-1
	PALMD	ENST00000605497.5	TSL:1	c.778C>G	p.Pro260Ala	missense	Exon 7 of 7	ENSP00000473839.1	S4R313
	PALMD	ENST00000496843.1	TSL:1	n.3937C>G		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461610 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727114

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111808

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	0.0074	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.083	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.9
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.22
Sift	Benign	0.058	T
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.56
MutPred		0.39		Loss of disorder (P = 0.1101)
MVP		0.75
MPC		0.24
ClinPred		0.92	D
GERP RS		5.8
Varity_R		0.098
gMVP		0.59
Mutation Taster		=87/13	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: rs144420060; hg19: chr1-100154594;