rs747511445

Variant names:

• chr19-46755682-C-G
• rs747511445
• NM_024301.5:c.232C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-46755682-C-G
• chr19-46755682-C-T

Variant summary

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

The NM_024301.5(FKRP):​c.232C>G​(p.Pro78Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FKRP NM_024301.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.69

Genes affected

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKRP	NM_024301.5	c.232C>G	p.Pro78Ala	missense_variant	Exon 4 of 4	ENST00000318584.10	NP_077277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKRP	ENST00000318584.10	c.232C>G	p.Pro78Ala	missense_variant	Exon 4 of 4	1	NM_024301.5	ENSP00000326570.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Uncertain	0.45	.;T;.;T;.;.;.;.;.;T
Eigen	Benign	-0.067
Eigen_PC	Benign	0.046
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T;.;T;T;T;T;T;T;T;T
M_CAP	Uncertain	0.27	D
MetaRNN	Uncertain	0.67	D;D;D;D;D;D;D;D;D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Benign	1.6	.;L;.;L;.;.;.;.;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.0	.;N;.;N;.;.;.;.;.;.
REVEL	Uncertain	0.54
Sift	Benign	0.13	.;T;.;T;.;.;.;.;.;.
Sift4G	Pathogenic	0.0	D;T;D;T;D;D;D;D;D;D
Polyphen		0.14	.;B;.;B;.;.;.;.;.;.
Vest4		0.43, 0.45
MutPred		0.56		Loss of loop (P = 0.0075);Loss of loop (P = 0.0075);Loss of loop (P = 0.0075);Loss of loop (P = 0.0075);Loss of loop (P = 0.0075);Loss of loop (P = 0.0075);Loss of loop (P = 0.0075);Loss of loop (P = 0.0075);Loss of loop (P = 0.0075);Loss of loop (P = 0.0075);
MVP		0.95
MPC		0.72
ClinPred		0.68	D
GERP RS		4.8
Varity_R		0.41
gMVP		0.60

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: rs747511445; hg19: chr19-47258939;