chr4-90308291-G-A

Variant names:

• chr4-90308291-G-A
• rs769598269
• NM_001145065.2:c.7G>A

Variant summary

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

The NM_001145065.2(CCSER1):​c.7G>A​(p.Asp3Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,028 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D3H) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: CCSER1 NM_001145065.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.22
• Publications: 0 publications found

Genes affected

CCSER1 (HGNC:29349): (coiled-coil serine rich protein 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145065.2. 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
	CCSER1	NM_001145065.2	MANE Select	c.7G>A	p.Asp3Asn	missense	Exon 2 of 11	NP_001138537.1	Q9C0I3-1
	CCSER1	NM_001377987.1		c.7G>A	p.Asp3Asn	missense	Exon 2 of 10	NP_001364916.1
	CCSER1	NM_207491.2		c.7G>A	p.Asp3Asn	missense	Exon 2 of 8	NP_997374.1	Q9C0I3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCSER1	ENST00000509176.6	TSL:1 MANE Select	c.7G>A	p.Asp3Asn	missense	Exon 2 of 11	ENSP00000425040.1	Q9C0I3-1
	CCSER1	ENST00000432775.6	TSL:1	c.7G>A	p.Asp3Asn	missense	Exon 2 of 8	ENSP00000389283.2	Q9C0I3-2
	CCSER1	ENST00000505073.5	TSL:1	n.7G>A		non_coding_transcript_exon	Exon 2 of 10	ENSP00000420964.1	E7EUW0

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152028 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152028 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74268

African (AFR) AF: 0.00 AC: 0 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.81	L
PhyloP100		9.2
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.21
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.26		Gain of glycosylation at S6 (P = 0.007)
MVP		0.41
MPC		0.39
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.58
gMVP		0.22
Mutation Taster		=76/24	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: rs769598269; hg19: chr4-91229442;