NM_001247997.2:c.3942G>C

Variant names:

• chr12-122278178-C-G
• rs1592957865
• NM_001247997.2:c.3942G>C

Variant summary

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

The NM_001247997.2(CLIP1):​c.3942G>C​(p.Glu1314Asp) 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: 30)
• Consequence: CLIP1 NM_001247997.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0380

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=0.14038798).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIP1	NM_001247997.2	c.3942G>C	p.Glu1314Asp	missense_variant	Exon 24 of 26	ENST00000620786.5	NP_001234926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIP1	ENST00000620786.5	c.3942G>C	p.Glu1314Asp	missense_variant	Exon 24 of 26	5	NM_001247997.2	ENSP00000479322.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3909G>C (p.E1303D) alteration is located in exon 23 (coding exon 22) of the CLIP1 gene. This alteration results from a G to C substitution at nucleotide position 3909, causing the glutamic acid (E) at amino acid position 1303 to be replaced by an aspartic acid (D). 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	0.081
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	.;.;.;.;T;.;.;T
Eigen	Benign	0.012
Eigen_PC	Benign	0.050
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.81	T;T;.;T;T;T;T;.
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.95	.;.;.;.;L;.;.;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.78	.;.;N;N;.;N;.;N
REVEL	Benign	0.091
Sift	Uncertain	0.013	.;.;D;D;.;D;.;D
Sift4G	Benign	0.11	T;.;T;T;T;T;.;T
Polyphen		0.83, 0.86	.;.;P;P;P;P;.;P
Vest4		0.18
MutPred		0.12		.;.;.;.;Loss of glycosylation at T1310 (P = 0.3649);.;.;Loss of glycosylation at T1310 (P = 0.3649);
MVP		0.51
MPC		1.5
ClinPred		0.59	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1592957865; hg19: chr12-122762725;