Genetic Variant SNTB2:c.*64_*65dupAA (chr16-69300977-C-CAA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_006750.4(SNTB2):c.*64_*65dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 881,324 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 0.00013 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0040 ( 0 hom. )

Consequence

SNTB2
NM_006750.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.169

Publications

1 publications found

Variant links:

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]

SNTB2 links:

ENSG00000260914 (HGNC:):

ENSG00000260914 links:

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ACMG classification

Classification was made for transcript

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

PM2

Variant has high frequency in the MID (0.00453) population. However there is too low homozygotes in high coverage region: (expected more than 2, got 0).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SNTB2	NM_006750.4	MANE Select	c.64_65dupAA	3_prime_UTR	Exon 7 of 7	NP_006741.1	Q13425-1
SNTB2	NR_172088.1		n.1776_1777dupAA	non_coding_transcript_exon	Exon 8 of 8
SNTB2	NR_172089.1		n.1677_1678dupAA	non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SNTB2	ENST00000336278.9	TSL:1 MANE Select	c.64_65dupAA	3_prime_UTR	Exon 7 of 7	ENSP00000338191.4	Q13425-1
ENSG00000260914	ENST00000570054.3	TSL:5	c.93+1214_93+1215dupAA	intron	N/A	ENSP00000461295.3	I3L4J1
SNTB2	ENST00000958019.1		c.64_65dupAA	3_prime_UTR	Exon 7 of 7	ENSP00000628078.1

Frequencies

GnomAD3 genomes

AF:

0.000133

AC:

AN:

142892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000630

Gnomad ASJ

AF:

0.00119

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000919

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00405

AC:

2989

AN:

738432

Hom.:

Cov.:

AF XY:

0.00410

AC XY:

1556

AN XY:

379950

show subpopulations

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

African (AFR)

AF:

0.00278

AC:

AN:

17242

American (AMR)

AF:

0.00214

AC:

AN:

23822

Ashkenazi Jewish (ASJ)

AF:

0.00502

AC:

AN:

17334

East Asian (EAS)

AF:

0.000661

AC:

AN:

28728

South Asian (SAS)

AF:

0.00214

AC:

119

AN:

55492

European-Finnish (FIN)

AF:

0.00213

AC:

AN:

39024

Middle Eastern (MID)

AF:

0.00506

AC:

AN:

3756

European-Non Finnish (NFE)

AF:

0.00469

AC:

2433

AN:

519116

Other (OTH)

AF:

0.00383

AC:

130

AN:

33918

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.272

Heterozygous variant carriers

272

544

817

1089

1361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

160

240

320

400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000133

AC:

AN:

142892

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

69098

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38870

American (AMR)

AF:

0.000630

AC:

AN:

14278

Ashkenazi Jewish (ASJ)

AF:

0.00119

AC:

AN:

3348

East Asian (EAS)

AF:

0.00

AC:

AN:

4932

South Asian (SAS)

AF:

0.00

AC:

AN:

4526

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8536

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.0000919

AC:

AN:

65282

Other (OTH)

AF:

0.00

AC:

AN:

1944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.17

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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16-69300977-CAAAA-CAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over