16-69245638-A-G

Variant names:

• chr16-69245638-A-G
• rs536615773
• NM_006750.4:c.617A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006750.4(SNTB2):​c.617A>G​(p.Lys206Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000427 in 1,614,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: SNTB2 NM_006750.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.09
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28626567).

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.617A>G	p.Lys206Arg	missense	Exon 2 of 7	NP_006741.1	Q13425-1
	SNTB2	NR_172088.1		n.706A>G		non_coding_transcript_exon	Exon 3 of 8
	SNTB2	NR_172089.1		n.607A>G		non_coding_transcript_exon	Exon 2 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNTB2	ENST00000336278.9	TSL:1 MANE Select	c.617A>G	p.Lys206Arg	missense	Exon 2 of 7	ENSP00000338191.4	Q13425-1
	SNTB2	ENST00000467311.5	TSL:1	n.617A>G		non_coding_transcript_exon	Exon 2 of 6	ENSP00000436443.1	Q13425-2
	SNTB2	ENST00000958019.1		c.617A>G	p.Lys206Arg	missense	Exon 2 of 7	ENSP00000628078.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152154 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251328 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000458 AC: 67 AN: 1461830 Hom.: 0 Cov.: 31 AF XY: 0.0000440 AC XY: 32 AN XY: 727210

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000513 AC: 57 AN: 1111968

Other (OTH) AF: 0.0000828 AC: 5 AN: 60382

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152272 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74462

African (AFR) AF: 0.00 AC: 0 AN: 41534

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.5	L
PhyloP100		7.1
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.16
Sift	Benign	0.24	T
Sift4G	Benign	0.48	T
Polyphen		0.89	P
Vest4		0.32
MutPred		0.32		Loss of ubiquitination at K206 (P = 0.0067)
MVP		0.78
MPC		0.35
ClinPred		0.52	D
GERP RS		4.6
Varity_R		0.15
gMVP		0.33
Mutation Taster		=67/33	polymorphism

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: rs536615773; hg19: chr16-69279541;