chr8-120575207-T-G

Position:

• chr8-120575207-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021021.4(SNTB1):​c.1015A>C​(p.Lys339Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNTB1 NM_021021.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.56

Genes affected

SNTB1 (HGNC:11168): (syntrophin beta 1) 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14540875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNTB1	NM_021021.4	c.1015A>C	p.Lys339Gln	missense_variant	4/7	ENST00000517992.2	NP_066301.1
SNTB1	XM_011517239.3	c.1015A>C	p.Lys339Gln	missense_variant	4/5		XP_011515541.1
SNTB1	XM_047422126.1	c.436A>C	p.Lys146Gln	missense_variant	4/7		XP_047278082.1
SNTB1	XM_047422127.1	c.436A>C	p.Lys146Gln	missense_variant	4/7		XP_047278083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNTB1	ENST00000517992.2	c.1015A>C	p.Lys339Gln	missense_variant	4/7	1	NM_021021.4	ENSP00000431124	P1
SNTB1	ENST00000519177.5	n.735A>C		non_coding_transcript_exon_variant	4/5	1
SNTB1	ENST00000395601.7	c.1015A>C	p.Lys339Gln	missense_variant	5/8	5		ENSP00000378965	P1
SNTB1	ENST00000648490.1	c.1015A>C	p.Lys339Gln	missense_variant, NMD_transcript_variant	4/8			ENSP00000497707

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.1015A>C (p.K339Q) alteration is located in exon 4 (coding exon 4) of the SNTB1 gene. This alteration results from a A to C substitution at nucleotide position 1015, causing the lysine (K) at amino acid position 339 to be replaced by a glutamine (Q). 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	0.070
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.68
DEOGEN2	Benign	0.32	T;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.19
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.30	N;N
REVEL	Benign	0.11
Sift	Benign	0.96	T;T
Sift4G	Benign	0.63	T;T
Polyphen		0.16	B;B
Vest4		0.32
MutPred		0.49		Loss of methylation at K339 (P = 0.0142);Loss of methylation at K339 (P = 0.0142);
MVP		0.16
ClinPred		0.98	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.43

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: rs758659001; hg19: chr8-121587447;