chr12-122278818-T-C

Variant names:

• chr12-122278818-T-C
• NM_001247997.2:c.3890A>G

Variant summary

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

The NM_001247997.2(CLIP1):​c.3890A>G​(p.Asn1297Ser) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLIP1 NM_001247997.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.77

Genes affected

CLIP1 (HGNC:10461): (CAP-Gly domain containing linker protein 1) The protein encoded by this gene links endocytic vesicles to microtubules. This gene is highly expressed in Reed-Sternberg cells of Hodgkin disease. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

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=0.110734314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIP1	NM_001247997.2	c.3890A>G	p.Asn1297Ser	missense_variant	Exon 23 of 26	ENST00000620786.5	NP_001234926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIP1	ENST00000620786.5	c.3890A>G	p.Asn1297Ser	missense_variant	Exon 23 of 26	5	NM_001247997.2	ENSP00000479322.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 02, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3857A>G (p.N1286S) alteration is located in exon 22 (coding exon 21) of the CLIP1 gene. This alteration results from a A to G substitution at nucleotide position 3857, causing the asparagine (N) at amino acid position 1286 to be replaced by a serine (S). 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	0.17
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	.;.;.;.;T;.;.;T
Eigen	Benign	0.032
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D;D;.;D;D;D;D;.
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.11	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	.;.;.;.;L;.;.;L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.68	.;.;N;N;.;N;.;N
REVEL	Benign	0.087
Sift	Benign	0.14	.;.;T;T;.;T;.;T
Sift4G	Benign	0.097	T;.;T;T;T;T;.;T
Polyphen		0.51, 0.21	.;.;P;P;B;P;.;B
Vest4		0.13
MutPred		0.093		.;.;.;.;Gain of phosphorylation at N1297 (P = 0.0155);.;.;Gain of phosphorylation at N1297 (P = 0.0155);
MVP		0.35
MPC		0.53
ClinPred		0.29	T
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.059
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr12-122763365;