rs779241531

Variant names:

• chr2-29135586-G-A
• rs779241531
• NM_024692.6:c.568G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-29135586-G-A
• chr2-29135586-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024692.6(CLIP4):​c.568G>A​(p.Ala190Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. A190P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CLIP4 NM_024692.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.64

Genes affected

CLIP4 (HGNC:26108): (CAP-Gly domain containing linker protein family member 4) Predicted to enable microtubule plus-end binding activity. Predicted to be involved in cytoplasmic microtubule organization. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.852

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIP4	NM_024692.6	c.568G>A	p.Ala190Thr	missense_variant	Exon 6 of 16	ENST00000320081.10	NP_078968.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIP4	ENST00000320081.10	c.568G>A	p.Ala190Thr	missense_variant	Exon 6 of 16	1	NM_024692.6	ENSP00000327009.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247668 Hom.: 0 AF XY: 0.00000747 AC XY: 1 AN XY: 133916

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000551

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458108 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725258

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.070	.;.;T;T;.;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;.;D;D;D
M_CAP	Benign	0.058	D
MetaRNN	Pathogenic	0.85	D;D;D;D;D;D
MetaSVM	Uncertain	0.25	D
MutationAssessor	Uncertain	2.8	M;.;M;M;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.5	N;N;D;D;D;D
REVEL	Uncertain	0.63
Sift	Uncertain	0.011	D;D;D;D;D;D
Sift4G	Uncertain	0.022	D;D;D;D;D;D
Polyphen		0.99	.;.;D;D;.;.
Vest4		0.65
MutPred		0.71		Gain of glycosylation at A190 (P = 0.0744);.;Gain of glycosylation at A190 (P = 0.0744);Gain of glycosylation at A190 (P = 0.0744);Gain of glycosylation at A190 (P = 0.0744);.;
MVP		0.91
MPC		0.45
ClinPred		0.94	D
GERP RS		4.5
Varity_R		0.37
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs779241531; hg19: chr2-29358452;