Genetic Variant NM_000023.4:c.34G>C (chr17-50166074-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000023.4(SGCA):c.34G>C(p.Val12Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V12M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

SGCA
NM_000023.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.293

Publications

0 publications found

Variant links:

Genes affected

SGCA (HGNC:10805): (sarcoglycan alpha) This gene encodes a component of the dystrophin-glycoprotein complex (DGC), which is critical to the stability of muscle fiber membranes and to the linking of the actin cytoskeleton to the extracellular matrix. Its expression is thought to be restricted to striated muscle. Mutations in this gene result in type 2D autosomal recessive limb-girdle muscular dystrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

SGCA Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, PanelApp Australia
autosomal recessive limb-girdle muscular dystrophy type 2D
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Orphanet

SGCA links:

ENSG00000253730 (HGNC:):

ENSG00000253730 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11895865).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000023.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SGCA	NM_000023.4	MANE Select	c.34G>C	p.Val12Leu	missense	Exon 1 of 10	NP_000014.1	A0A0S2Z4Q1
SGCA	NM_001135697.3		c.34G>C	p.Val12Leu	missense	Exon 1 of 8	NP_001129169.1	A0A0S2Z4P8
SGCA	NR_135553.2		n.70G>C		non_coding_transcript_exon	Exon 1 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SGCA	ENST00000262018.8	TSL:1 MANE Select	c.34G>C	p.Val12Leu	missense	Exon 1 of 10	ENSP00000262018.3	Q16586-1
SGCA	ENST00000344627.10	TSL:1	c.34G>C	p.Val12Leu	missense	Exon 1 of 8	ENSP00000345522.6	Q16586-2
SGCA	ENST00000952408.1		c.34G>C	p.Val12Leu	missense	Exon 1 of 10	ENSP00000622467.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.26

CADD

Benign

0.17

(source)

DANN

Benign

0.67

DEOGEN2

Uncertain

0.61

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.49

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.12

MetaSVM

Uncertain

0.046

MutationAssessor

Benign

1.4

PhyloP100

-0.29

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.030

REVEL

Uncertain

0.33

Sift

Benign

0.85

Sift4G

Benign

0.19

Polyphen

0.0

Vest4

0.13

MutPred

0.53

Gain of helix (P = 0.0078)

MVP

0.90

MPC

0.33

ClinPred

0.025

GERP RS

0.19

PromoterAI

0.069

Neutral

(source)

Varity_R

0.051

gMVP

0.41

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over