rs10044666

Variant names:

• chr5-155749010-G-T
• rs10044666
• XM_017009724.2:c.-208+20020G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000755060.1(ENSG00000298352):​n.471+20020G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,088 control chromosomes in the GnomAD database, including 4,549 homozygotes. 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: 𝑓 0.24 (4549 hom., cov: 32)
• Consequence: ENSG00000298352 ENST00000755060.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452
• Publications: 3 publications found

Genes affected

SGCD (HGNC:10807): (sarcoglycan delta) The protein encoded by this gene is one of the four known components of the sarcoglycan complex, which is a subcomplex of the dystrophin-glycoprotein complex (DGC). DGC forms a link between the F-actin cytoskeleton and the extracellular matrix. This protein is expressed most abundantly in skeletal and cardiac muscle. Mutations in this gene have been associated with autosomal recessive limb-girdle muscular dystrophy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding distinct isoforms have been observed for this gene. [provided by RefSeq, Jul 2008]

SGCD Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2F

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Myriad Women's Health, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• dilated cardiomyopathy 1L

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

ENSG00000298352 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000755060.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000298352	ENST00000755060.1		n.471+20020G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36385 AN: 151970 Hom.: 4546 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.230

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.239 AC: 36406 AN: 152088 Hom.: 4549 Cov.: 32 AF XY: 0.241 AC XY: 17901 AN XY: 74338

African (AFR) AF: 0.201 AC: 8339 AN: 41486

American (AMR) AF: 0.203 AC: 3104 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 552 AN: 3470

East Asian (EAS) AF: 0.234 AC: 1212 AN: 5174

South Asian (SAS) AF: 0.417 AC: 2008 AN: 4814

European-Finnish (FIN) AF: 0.231 AC: 2447 AN: 10582

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18016 AN: 67978

Other (OTH) AF: 0.233 AC: 492 AN: 2110

Alfa AF: 0.252 Hom.: 18433

Bravo AF: 0.230

Asia WGS AF: 0.350 AC: 1217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.71
DANN	Benign	0.85
PhyloP100		-0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10044666;

hg19: chr5-155128570;

COSMIC: COSV60219189;