NM_016472.5:c.182A>C

Variant names:

• chr14-96382429-A-C
• NM_016472.5:c.182A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016472.5(GSKIP):​c.182A>C​(p.Asp61Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,082 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000014 (0 hom.)
• Consequence: GSKIP NM_016472.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.57
• Publications: 0 publications found

Genes affected

GSKIP (HGNC:20343): (GSK3B interacting protein) This gene encodes a protein that is involved as a negative regulator of GSK3-beta in the Wnt signaling pathway. The encoded protein may play a role in the retinoic acid signaling pathway by regulating the functional interactions between GSK3-beta, beta-catenin and cyclin D1, and it regulates the beta-catenin/N-cadherin pool. The encoded protein contains a GSK3-beta interacting domain (GID) in its C-terminus, which is similar to the GID of Axin. The protein also contains an evolutionarily conserved RII-binding domain, which facilitates binding with protein kinase-A and GSK3-beta, enabling its role as an A-kinase anchoring protein. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2012]

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=0.0797379).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016472.5. 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
	GSKIP	NM_016472.5	MANE Select	c.182A>C	p.Asp61Ala	missense	Exon 3 of 4	NP_057556.2	Q9P0R6
	GSKIP	NM_001271904.1		c.182A>C	p.Asp61Ala	missense	Exon 3 of 4	NP_001258833.1	Q9P0R6
	GSKIP	NM_001271905.2		c.182A>C	p.Asp61Ala	missense	Exon 3 of 4	NP_001258834.1	Q9P0R6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSKIP	ENST00000555181.6	TSL:1 MANE Select	c.182A>C	p.Asp61Ala	missense	Exon 3 of 4	ENSP00000450420.1	Q9P0R6
	GSKIP	ENST00000438650.5	TSL:2	c.182A>C	p.Asp61Ala	missense	Exon 2 of 3	ENSP00000412315.1	Q9P0R6
	GSKIP	ENST00000554182.5	TSL:2	c.182A>C	p.Asp61Ala	missense	Exon 3 of 4	ENSP00000451384.1	Q9P0R6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461082 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726874

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111310

Other (OTH) AF: 0.00 AC: 0 AN: 60364

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	0.10
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Benign	0.81
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.58	N
PhyloP100		2.6
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.047
Sift	Benign	0.79	T
Sift4G	Benign	0.30	T
Polyphen		0.0070	B
Vest4		0.27
MutPred		0.41		Gain of catalytic residue at D62 (P = 0.0026)
MVP		0.12
MPC		0.58
ClinPred		0.36	T
GERP RS		5.7
Varity_R		0.089
gMVP		0.29
Mutation Taster		=84/16	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: chr14-96848766;