6-7369956-C-T

Variant names:

• chr6-7369956-C-T
• rs1319398521
• NM_001170692.2:c.1856G>A

Variant summary

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

The NM_001170692.2(CAGE1):​c.1856G>A​(p.Ser619Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. S619T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CAGE1 NM_001170692.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 0 publications found

Genes affected

CAGE1 (HGNC:21622): (cancer antigen 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=0.080847114).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170692.2. 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
	CAGE1	NM_001170692.2	MANE Select	c.1856G>A	p.Ser619Asn	missense	Exon 6 of 14	NP_001164163.1	Q8TC20-5
	CAGE1	NM_001170693.2		c.1856G>A	p.Ser619Asn	missense	Exon 6 of 13	NP_001164164.1	Q8TC20-3
	CAGE1	NM_205864.3		c.1448G>A	p.Ser483Asn	missense	Exon 5 of 11	NP_995586.1	Q8TC20-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAGE1	ENST00000502583.6	TSL:5 MANE Select	c.1856G>A	p.Ser619Asn	missense	Exon 6 of 14	ENSP00000425493.1	Q8TC20-5
	CAGE1	ENST00000338150.8	TSL:2	c.1856G>A	p.Ser619Asn	missense	Exon 6 of 13	ENSP00000338107.4	Q8TC20-3
	CAGE1	ENST00000379918.8	TSL:5	c.1856G>A	p.Ser619Asn	missense	Exon 6 of 14	ENSP00000369250.4	E7EUJ7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461472 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727022

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44682

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111784

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.019
DANN	Benign	0.12
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.8
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.012
Sift	Benign	0.57	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.20		Loss of ubiquitination at K616 (P = 0.0435)
MVP		0.16
MPC		0.098
ClinPred		0.034	T
GERP RS		-1.9
Varity_R		0.036
gMVP		0.045
Mutation Taster		=100/0	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

dbSNP: rs1319398521; hg19: chr6-7370189;