1-110041791-A-G

Position:

• chr1-110041791-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_033088.4(STRIP1):​c.815A>G​(p.Lys272Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: STRIP1 NM_033088.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.91

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.796

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRIP1	NM_033088.4	c.815A>G	p.Lys272Arg	missense_variant	8/21	ENST00000369795.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRIP1	ENST00000369795.8	c.815A>G	p.Lys272Arg	missense_variant	8/21	1	NM_033088.4	P1
STRIP1	ENST00000485775.5	c.*290A>G		3_prime_UTR_variant, NMD_transcript_variant	9/22	1
STRIP1	ENST00000369796.5	c.530A>G	p.Lys177Arg	missense_variant	8/21	2
STRIP1	ENST00000473429.5	n.621A>G		non_coding_transcript_exon_variant	1/14	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.087
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.0068	T
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.26
Sift	Benign	0.44	T;T
Sift4G	Benign	0.32	T;T
Polyphen		1.0	D;D
Vest4		0.76
MutPred		0.65		.;Loss of methylation at K272 (P = 0.0114);
MVP		0.47
MPC		0.98
ClinPred		0.86	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1652776723; hg19: chr1-110584413;