rs759105985

Variant names:

• chr4-168898595-G-A
• NM_001166108.2:c.2353G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-168898595-G-A
• chr4-168898595-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001166108.2(PALLD):​c.2353G>A​(p.Asp785Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PALLD NM_001166108.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.15

Genes affected

PALLD (HGNC:17068): (palladin, cytoskeletal associated protein) This gene encodes a cytoskeletal protein that is required for organizing the actin cytoskeleton. The protein is a component of actin-containing microfilaments, and it is involved in the control of cell shape, adhesion, and contraction. Polymorphisms in this gene are associated with a susceptibility to pancreatic cancer type 1, and also with a risk for myocardial infarction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

CBR4 (HGNC:25891): (carbonyl reductase 4) Enables several functions, including 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity; NADPH binding activity; and NADPH dehydrogenase (quinone) activity. Involved in fatty acid biosynthetic process; glycoside metabolic process; and protein tetramerization. Located in mitochondrial matrix. Part of oxidoreductase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33504766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALLD	NM_001166108.2	c.2353G>A	p.Asp785Asn	missense_variant	Exon 14 of 22	ENST00000505667.6	NP_001159580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALLD	ENST00000505667.6	c.2353G>A	p.Asp785Asn	missense_variant	Exon 14 of 22	1	NM_001166108.2	ENSP00000425556.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461354 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727006

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.061	.;.;.;.;T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.21
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	D;T;D;D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.34	T;T;T;T;T;T
MetaSVM	Benign	-0.82	T
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.3	N;D;N;D;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0070	D;D;T;D;T;T
Sift4G	Benign	0.10	T;T;T;D;D;D
Vest4		0.30
MVP		0.69
MPC		0.35
ClinPred		0.84	D
GERP RS		4.7
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr4-169819746;