16-69300977-CAAAA-CA

Variant names:

• chr16-69300977-CAAA-C
• rs34703750
• NM_006750.4:c.*63_*65delAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006750.4(SNTB2):​c.*63_*65delAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000377 in 741,782 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000038 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SNTB2 NM_006750.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78
• Publications: 0 publications found

Genes affected

SNTB2 (HGNC:11169): (syntrophin beta 2) Dystrophin is a large, rod-like cytoskeletal protein found at the inner surface of muscle fibers. Dystrophin is missing in Duchenne Muscular Dystrophy patients and is present in reduced amounts in Becker Muscular Dystrophy patients. The protein encoded by this gene is a peripheral membrane protein found associated with dystrophin and dystrophin-related proteins. This gene is a member of the syntrophin gene family, which contains at least two other structurally-related genes. [provided by RefSeq, Jul 2008]

ENSG00000260914 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006750.4. 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
	SNTB2	NM_006750.4	MANE Select	c.*63_*65delAAA		3_prime_UTR	Exon 7 of 7	NP_006741.1	Q13425-1
	SNTB2	NR_172088.1		n.1775_1777delAAA		non_coding_transcript_exon	Exon 8 of 8
	SNTB2	NR_172089.1		n.1676_1678delAAA		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNTB2	ENST00000336278.9	TSL:1 MANE Select	c.*63_*65delAAA		3_prime_UTR	Exon 7 of 7	ENSP00000338191.4	Q13425-1
	ENSG00000260914	ENST00000570054.3	TSL:5	c.93+1213_93+1215delAAA		intron	N/A	ENSP00000461295.3	I3L4J1
	SNTB2	ENST00000958019.1		c.*63_*65delAAA		3_prime_UTR	Exon 7 of 7	ENSP00000628078.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 142890 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

GnomAD4 exome AF: 0.0000377 AC: 28 AN: 741782 Hom.: 0 AF XY: 0.0000314 AC XY: 12 AN XY: 381708

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000116 AC: 2 AN: 17304

American (AMR) AF: 0.0000837 AC: 2 AN: 23904

Ashkenazi Jewish (ASJ) AF: 0.0000574 AC: 1 AN: 17436

East Asian (EAS) AF: 0.00 AC: 0 AN: 28802

South Asian (SAS) AF: 0.0000359 AC: 2 AN: 55726

European-Finnish (FIN) AF: 0.000102 AC: 4 AN: 39192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3772

European-Non Finnish (NFE) AF: 0.0000326 AC: 17 AN: 521566

Other (OTH) AF: 0.00 AC: 0 AN: 34080

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 142890 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 69096

African (AFR) AF: 0.00 AC: 0 AN: 38870

American (AMR) AF: 0.00 AC: 0 AN: 14278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3348

East Asian (EAS) AF: 0.00 AC: 0 AN: 4932

South Asian (SAS) AF: 0.00 AC: 0 AN: 4526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65282

Other (OTH) AF: 0.00 AC: 0 AN: 1944

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8

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

Other links and lift over

dbSNP: rs34703750; hg19: chr16-69334880;