16-69300977-CAAAA-CAAAAAAA

Variant names:

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

Variant summary

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

The NM_006750.4(SNTB2):​c.*63_*65dupAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000512 in 741,980 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: not found (cov: 29)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: SNTB2 NM_006750.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• 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_*65dupAAA		3_prime_UTR	Exon 7 of 7	NP_006741.1	Q13425-1
	SNTB2	NR_172088.1		n.1775_1777dupAAA		non_coding_transcript_exon	Exon 8 of 8
	SNTB2	NR_172089.1		n.1676_1678dupAAA		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_*65dupAAA		3_prime_UTR	Exon 7 of 7	ENSP00000338191.4	Q13425-1
	ENSG00000260914	ENST00000570054.3	TSL:5	c.93+1213_93+1215dupAAA		intron	N/A	ENSP00000461295.3	I3L4J1
	SNTB2	ENST00000958019.1		c.*63_*65dupAAA		3_prime_UTR	Exon 7 of 7	ENSP00000628078.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.0000512 AC: 38 AN: 741980 Hom.: 0 Cov.: 6 AF XY: 0.0000419 AC XY: 16 AN XY: 381818

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

African (AFR) AF: 0.0000578 AC: 1 AN: 17302

American (AMR) AF: 0.00 AC: 0 AN: 23914

Ashkenazi Jewish (ASJ) AF: 0.0000573 AC: 1 AN: 17440

East Asian (EAS) AF: 0.00 AC: 0 AN: 28824

South Asian (SAS) AF: 0.0000359 AC: 2 AN: 55734

European-Finnish (FIN) AF: 0.0000510 AC: 2 AN: 39190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3774

European-Non Finnish (NFE) AF: 0.0000537 AC: 28 AN: 521712

Other (OTH) AF: 0.000117 AC: 4 AN: 34090

⚠️ 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 Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.17

Splicing

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

Other links and lift over

dbSNP: rs34703750; hg19: chr16-69334880;