4-90308291-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001145065.2(CCSER1):c.7G>C(p.Asp3His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCSER1 NM_001145065.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.22

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCSER1	NM_001145065.2	c.7G>C	p.Asp3His	missense_variant	2/11	ENST00000509176.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCSER1	ENST00000509176.6	c.7G>C	p.Asp3His	missense_variant	2/11	1	NM_001145065.2	P1
CCSER1	ENST00000432775.6	c.7G>C	p.Asp3His	missense_variant	2/8	1
CCSER1	ENST00000505073.5	c.7G>C	p.Asp3His	missense_variant, NMD_transcript_variant	2/10	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000832 AC: 1

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

Dec 07, 2023

The c.7G>C (p.D3H) alteration is located in exon 2 (coding exon 1) of the CCSER1 gene. This alteration results from a G to C substitution at nucleotide position 7, causing the aspartic acid (D) at amino acid position 3 to be replaced by a histidine (H). 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	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
Cadd	Pathogenic	29
Dann	Uncertain	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	0.95	D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	0.81	L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		1.0	D;D
Vest4		0.72
MutPred		0.28		Gain of glycosylation at S6 (P = 0.007);Gain of glycosylation at S6 (P = 0.007);
MVP		0.47
MPC		0.42
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.78
gMVP		0.32

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

LitVar

Other links and lift over

dbSNP: rs769598269; hg19: chr4-91229442;