19-46746099-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_013403.3(STRN4):c.282+50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000896 in 1,395,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: STRN4 NM_013403.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18

Genes affected

STRN4 (HGNC:15721): (striatin 4) Enables armadillo repeat domain binding activity and protein phosphatase 2A binding activity. Part of FAR/SIN/STRIPAK complex. [provided by Alliance of Genome Resources, Apr 2022]

FKRP (HGNC:17997): (fukutin related protein) This gene encodes a protein which is targeted to the medial Golgi apparatus and is necessary for posttranslational modification of dystroglycan. Mutations in this gene have been associated with congenital muscular dystrophy, cognitive disability, and cerebellar cysts. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 19-46746099-G-A is Benign according to our data. Variant chr19-46746099-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 509026.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 71 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRN4	NM_013403.3	c.282+50C>T		intron_variant		ENST00000263280.11
FKRP	NM_024301.5	c.-253+9G>A		intron_variant		ENST00000318584.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRN4	ENST00000263280.11	c.282+50C>T		intron_variant		1	NM_013403.3	P4
FKRP	ENST00000318584.10	c.-253+9G>A		intron_variant		1	NM_024301.5	P1

Frequencies

GnomAD3 genomes AF: 0.000475 AC: 71 AN: 149490 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000198

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000484

GnomAD4 exome AF: 0.0000433 AC: 54 AN: 1245890 Hom.: 0 Cov.: 34 AF XY: 0.0000342 AC XY: 21 AN XY: 613192

Gnomad4 AFR exome AF: 0.00183

Gnomad4 AMR exome AF: 0.000111

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: 0.00000397

Gnomad4 OTH exome AF: 0.0000797

GnomAD4 genome AF: 0.000475 AC: 71 AN: 149600 Hom.: 0 Cov.: 30 AF XY: 0.000479 AC XY: 35 AN XY: 73112

Gnomad4 AFR AF: 0.00166

Gnomad4 AMR AF: 0.000198

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000479

Bravo AF: 0.000635

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	13
Dann	Benign	0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6

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

LitVar

Other links and lift over

dbSNP: rs571064207; hg19: chr19-47249356; COSMIC: COSV54422305; COSMIC: COSV54422305;