rs754347622

Variant names:

• chr19-46756156-C-A
• NM_024301.5:c.706C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-46756156-C-A
• chr19-46756156-C-G
• chr19-46756156-C-T

Variant summary

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

The NM_024301.5(FKRP):​c.706C>A​(p.Leu236Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000761 in 1,314,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: FKRP NM_024301.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40637952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKRP	NM_024301.5	c.706C>A	p.Leu236Met	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.706C>A	p.Leu236Met	missense_variant	Exon 4 of 4	1	NM_024301.5	ENSP00000326570.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.61e-7 AC: 1 AN: 1314112 Hom.: 0 Cov.: 32 AF XY: 0.00000155 AC XY: 1 AN XY: 647098

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000453

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.35	T;T
Eigen	Benign	0.046
Eigen_PC	Benign	0.050
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.37	.;T
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	1.7	L;L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.84	N;N
REVEL	Uncertain	0.58
Sift	Benign	0.10	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.65	P;P
Vest4		0.32
MutPred		0.38		Gain of catalytic residue at L236 (P = 0.0013);Gain of catalytic residue at L236 (P = 0.0013);
MVP		0.80
MPC		0.68
ClinPred		0.70	D
GERP RS		4.1
Varity_R		0.41
gMVP		0.71

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: chr19-47259413;