16-2179083-C-T

Position:

• chr16-2179083-C-T

Variant summary

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

The NM_020764.4(CASKIN1):​c.4018G>A​(p.Ala1340Thr) 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. 14/21 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CASKIN1 NM_020764.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.360

Genes affected

CASKIN1 (HGNC:20879): (CASK interacting protein 1) Enables identical protein binding activity. Predicted to be involved in signal transduction. Predicted to be active in cytoplasm and membrane. [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=0.092645615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASKIN1	NM_020764.4	c.4018G>A	p.Ala1340Thr	missense_variant	19/20	ENST00000343516.8	NP_065815.1
CASKIN1	XM_024450361.2	c.3805G>A	p.Ala1269Thr	missense_variant	17/18		XP_024306129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASKIN1	ENST00000343516.8	c.4018G>A	p.Ala1340Thr	missense_variant	19/20	1	NM_020764.4	ENSP00000345436.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 839000 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 388434

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: 0.00

Gnomad4 OTH exome AF: 0.00

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

Feb 16, 2023

The c.4018G>A (p.A1340T) alteration is located in exon 19 (coding exon 19) of the CASKIN1 gene. This alteration results from a G to A substitution at nucleotide position 4018, causing the alanine (A) at amino acid position 1340 to be replaced by a threonine (T). 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	0.083
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.84
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.46	T
M_CAP	Pathogenic	0.59	D
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.32	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.036
Sift	Benign	0.11	T
Sift4G	Benign	0.51	T
Polyphen		0.0	B
Vest4		0.093
MutPred		0.26		Gain of glycosylation at A1340 (P = 2e-04);
MVP		0.47
MPC		0.27
ClinPred		0.093	T
GERP RS		0.96
Varity_R		0.030
gMVP		0.28

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: chr16-2229084;