chr17-4988511-C-A

Variant names:

• chr17-4988511-C-A
• rs868274019
• NM_001394789.1:c.605G>T

Variant summary

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

The NM_001394789.1(INCA1):​c.605G>T​(p.Cys202Phe) 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. 15/21 in silico tools predict a benign outcome for this variant. 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. C202Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: INCA1 NM_001394789.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235
• Publications: 1 publications found

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:55342): (CAMTA2 antisense RNA 1)

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=0.100138664).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394789.1. 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
	INCA1	NM_001394789.1	MANE Select	c.605G>T	p.Cys202Phe	missense	Exon 7 of 7	NP_001381718.1	Q0VD86-1
	INCA1	NM_001167986.2		c.605G>T	p.Cys202Phe	missense	Exon 9 of 9	NP_001161458.1	Q0VD86-1
	INCA1	NM_001167987.2		c.605G>T	p.Cys202Phe	missense	Exon 8 of 8	NP_001161459.1	Q0VD86-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INCA1	ENST00000695324.1	MANE Select	c.605G>T	p.Cys202Phe	missense	Exon 7 of 7	ENSP00000511805.1	Q0VD86-1
	INCA1	ENST00000574617.1	TSL:1	c.605G>T	p.Cys202Phe	missense	Exon 8 of 8	ENSP00000458316.1	Q0VD86-1
	INCA1	ENST00000576820.5	TSL:1	c.605G>T	p.Cys202Phe	missense	Exon 7 of 7	ENSP00000460673.1	Q0VD86-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.23
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Benign	0.13
Sift	Benign	0.090	T
Sift4G	Benign	0.11	T
Polyphen		0.24	B
Vest4		0.17
MutPred		0.27		Gain of helix (P = 0.0425)
MVP		0.12
ClinPred		0.13	T
GERP RS		1.3
Varity_R		0.13
gMVP		0.050

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

Other links and lift over

dbSNP: rs868274019; hg19: chr17-4891806;