4-90309222-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145065.2(CCSER1):c.938C>T(p.Thr313Ile) 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. 14/21 in silico tools predict a benign outcome for this variant. 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: 0.986

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08286461).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCSER1	NM_001145065.2	c.938C>T	p.Thr313Ile	missense_variant	2/11	ENST00000509176.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCSER1	ENST00000509176.6	c.938C>T	p.Thr313Ile	missense_variant	2/11	1	NM_001145065.2	P1
CCSER1	ENST00000432775.6	c.938C>T	p.Thr313Ile	missense_variant	2/8	1
CCSER1	ENST00000505073.5	c.938C>T	p.Thr313Ile	missense_variant, NMD_transcript_variant	2/10	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Jun 30, 2023

The c.938C>T (p.T313I) alteration is located in exon 2 (coding exon 1) of the CCSER1 gene. This alteration results from a C to T substitution at nucleotide position 938, causing the threonine (T) at amino acid position 313 to be replaced by an isoleucine (I). 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	Benign	0.099
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	7.4
Dann	Uncertain	0.98
DEOGEN2	Benign	0.039	T;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.083	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.011
Sift	Benign	0.073	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.0010	B;B
Vest4		0.060
MutPred		0.27		Loss of disorder (P = 0.0213);Loss of disorder (P = 0.0213);
MVP		0.067
MPC		0.067
ClinPred		0.083	T
GERP RS		1.9
Varity_R		0.041
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-91230373;