17-4990249-T-C

Position:

• chr17-4990249-T-C

Variant summary

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

The NM_001394789.1(INCA1):​c.61A>G​(p.Ser21Gly) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: INCA1 NM_001394789.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0540

Genes affected

INCA1 (HGNC:32224): (inhibitor of CDK, cyclin A1 interacting protein 1) Enables cyclin binding activity; cyclin-dependent protein serine/threonine kinase inhibitor activity; and identical protein binding activity. Acts upstream of or within negative regulation of cyclin-dependent protein serine/threonine kinase activity. Located in cytoplasm and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

CAMTA2-AS1 (HGNC:):

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=0.31767952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INCA1	NM_001394789.1	c.61A>G	p.Ser21Gly	missense_variant	3/7	ENST00000695324.1	NP_001381718.1
CAMTA2-AS1	XR_001752769.2	n.3149T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INCA1	ENST00000695324.1	c.61A>G	p.Ser21Gly	missense_variant	3/7		NM_001394789.1	ENSP00000511805	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

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

Apr 05, 2023

The c.61A>G (p.S21G) alteration is located in exon 5 (coding exon 2) of the INCA1 gene. This alteration results from a A to G substitution at nucleotide position 61, causing the serine (S) at amino acid position 21 to be replaced by a glycine (G). 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	0.17
BayesDel_addAF	Benign	-0.0037	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	.;.;T;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.65	.;T;.;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.90	L;L;L;L
MutationTaster	Benign	0.58	N;N;N;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.0	D;.;.;.
REVEL	Benign	0.21
Sift	Uncertain	0.025	D;.;.;.
Sift4G	Uncertain	0.030	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.31
MutPred		0.26		Loss of phosphorylation at S21 (P = 0.0065);Loss of phosphorylation at S21 (P = 0.0065);Loss of phosphorylation at S21 (P = 0.0065);Loss of phosphorylation at S21 (P = 0.0065);
MVP		0.37
ClinPred		0.97	D
GERP RS		4.4
Varity_R		0.31
gMVP		0.12

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: chr17-4893544;