7-74338807-G-T

Variant names:

• chr7-74338807-G-T
• NM_003388.5:c.481G>T

Variant summary

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

The NM_003388.5(CLIP2):​c.481G>T​(p.Val161Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CLIP2 NM_003388.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.87

Genes affected

CLIP2 (HGNC:2586): (CAP-Gly domain containing linker protein 2) The protein encoded by this gene belongs to the family of cytoplasmic linker proteins, which have been proposed to mediate the interaction between specific membranous organelles and microtubules. This protein was found to associate with both microtubules and an organelle called the dendritic lamellar body. This gene is hemizygously deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Alternative splicing of this gene generates 2 transcript variants. [provided by RefSeq, Jul 2008]

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=0.21825364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIP2	NM_003388.5	c.481G>T	p.Val161Leu	missense_variant	Exon 3 of 17	ENST00000223398.11	NP_003379.4
CLIP2	NM_032421.3	c.481G>T	p.Val161Leu	missense_variant	Exon 3 of 16		NP_115797.2
CLIP2	XM_047420800.1	c.481G>T	p.Val161Leu	missense_variant	Exon 3 of 13		XP_047276756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIP2	ENST00000223398.11	c.481G>T	p.Val161Leu	missense_variant	Exon 3 of 17	5	NM_003388.5	ENSP00000223398.6
CLIP2	ENST00000361545.9	c.481G>T	p.Val161Leu	missense_variant	Exon 3 of 16	1		ENSP00000355151.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458932 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725928

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	0.0031	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.090	.;T;T
Eigen	Benign	0.19
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.93	D;D;.
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.81	L;L;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.21
Sift	Benign	0.23	T;T;T
Sift4G	Benign	0.27	T;T;T
Polyphen		0.91	P;P;P
Vest4		0.27
MutPred		0.16		Gain of phosphorylation at S160 (P = 0.1943);Gain of phosphorylation at S160 (P = 0.1943);Gain of phosphorylation at S160 (P = 0.1943);
MVP		0.76
MPC		0.79
ClinPred		0.75	D
GERP RS		4.6
Varity_R		0.090
gMVP		0.29

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: chr7-73753137;