chr1-110039266-G-T

Position:

• chr1-110039266-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033088.4(STRIP1):​c.420G>T​(p.Lys140Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000109 in 1,461,888 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: STRIP1 NM_033088.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.75

Genes affected

STRIP1 (HGNC:25916): (striatin interacting protein 1) This gene encodes a member of the striatin-interacting phosphatase and kinase complex, which is involved in localization of the Golgi body. The encoded protein participates in cytosketelal organization. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33640146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRIP1	NM_033088.4	c.420G>T	p.Lys140Asn	missense_variant	4/21	ENST00000369795.8	NP_149079.2
STRIP1	NM_001270768.2	c.135G>T	p.Lys45Asn	missense_variant	4/21		NP_001257697.1
STRIP1	XM_047432935.1	c.420G>T	p.Lys140Asn	missense_variant	4/11		XP_047288891.1
STRIP1	NR_073071.2	n.434G>T		non_coding_transcript_exon_variant	4/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRIP1	ENST00000369795.8	c.420G>T	p.Lys140Asn	missense_variant	4/21	1	NM_033088.4	ENSP00000358810	P1
STRIP1	ENST00000485775.5	c.420G>T	p.Lys140Asn	missense_variant, NMD_transcript_variant	4/22	1		ENSP00000476025
STRIP1	ENST00000369796.5	c.135G>T	p.Lys45Asn	missense_variant	4/21	2		ENSP00000358811
STRIP1	ENST00000540970.1	n.173G>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8 AN XY: 727248

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: 0.0000144

Gnomad4 OTH exome AF: 0.00

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

Jan 17, 2023

The c.420G>T (p.K140N) alteration is located in exon 4 (coding exon 4) of the STRIP1 gene. This alteration results from a G to T substitution at nucleotide position 420, causing the lysine (K) at amino acid position 140 to be replaced by an asparagine (N). 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	Uncertain	0.45
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.087	.;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.28
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.11
Sift	Benign	0.38	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.19	.;B
Vest4		0.57
MutPred		0.51		.;Loss of ubiquitination at K140 (P = 0.0297);
MVP		0.17
MPC		0.43
ClinPred		0.31	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.50

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: chr1-110581888;