chr16-69245716-G-C

Variant names:

• chr16-69245716-G-C
• rs909917963
• NM_006750.4:c.695G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006750.4(SNTB2):​c.695G>C​(p.Gly232Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,884 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: SNTB2 NM_006750.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.18

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36548507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNTB2	NM_006750.4	c.695G>C	p.Gly232Ala	missense_variant	Exon 2 of 7	ENST00000336278.9	NP_006741.1
SNTB2	NR_172088.1	n.784G>C		non_coding_transcript_exon_variant	Exon 3 of 8
SNTB2	NR_172089.1	n.685G>C		non_coding_transcript_exon_variant	Exon 2 of 7
SNTB2	NR_172090.1	n.698G>C		non_coding_transcript_exon_variant	Exon 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNTB2	ENST00000336278.9	c.695G>C	p.Gly232Ala	missense_variant	Exon 2 of 7	1	NM_006750.4	ENSP00000338191.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 727240

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.695G>C (p.G232A) alteration is located in exon 2 (coding exon 2) of the SNTB2 gene. This alteration results from a G to C substitution at nucleotide position 695, causing the glycine (G) at amino acid position 232 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	0.0079	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.13
Sift	Benign	0.86	T
Sift4G	Benign	0.97	T
Polyphen		0.87	P
Vest4		0.51
MutPred		0.21		Gain of relative solvent accessibility (P = 0.0479);
MVP		0.67
MPC		0.92
ClinPred		0.79	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.090
gMVP		0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs909917963; hg19: chr16-69279619;