4-90308376-C-T

Variant names:

• chr4-90308376-C-T
• rs1007696750
• NM_001145065.2:c.92C>T

Variant summary

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

The NM_001145065.2(CCSER1):​c.92C>T​(p.Ser31Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,430 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. S31Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCSER1 NM_001145065.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.28
• 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.92C>T	p.Ser31Phe	missense	Exon 2 of 11	NP_001138537.1	Q9C0I3-1
	CCSER1	NM_001377987.1		c.92C>T	p.Ser31Phe	missense	Exon 2 of 10	NP_001364916.1
	CCSER1	NM_207491.2		c.92C>T	p.Ser31Phe	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.92C>T	p.Ser31Phe	missense	Exon 2 of 11	ENSP00000425040.1	Q9C0I3-1
	CCSER1	ENST00000432775.6	TSL:1	c.92C>T	p.Ser31Phe	missense	Exon 2 of 8	ENSP00000389283.2	Q9C0I3-2
	CCSER1	ENST00000505073.5	TSL:1	n.92C>T		non_coding_transcript_exon	Exon 2 of 10	ENSP00000420964.1	E7EUW0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461430 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726970

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111788

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	0.97	L
PhyloP100		7.3
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.51
MutPred		0.22		Loss of glycosylation at P33 (P = 0.0046)
MVP		0.61
MPC		0.41
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.74
gMVP		0.47
Mutation Taster		=46/54	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1007696750; hg19: chr4-91229527; COSMIC: COSV105883056; COSMIC: COSV105883056;