16-69187182-G-C

Variant names:

• chr16-69187182-G-C
• NM_006750.4:c.16G>C

Variant summary

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

The NM_006750.4(SNTB2):​c.16G>C​(p.Ala6Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SNTB2 NM_006750.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63

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]

UTP4 (HGNC:1983): (UTP4 small subunit processome component) This gene encodes a WD40-repeat-containing protein that is localized to the nucleolus. Mutation of this gene causes North American Indian childhood cirrhosis, a severe intrahepatic cholestasis that results in transient neonatal jaundice, and progresses to periportal fibrosis and cirrhosis in childhood and adolescence. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

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=0.27709627).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNTB2	NM_006750.4	c.16G>C	p.Ala6Pro	missense_variant	Exon 1 of 7	ENST00000336278.9	NP_006741.1
SNTB2	NR_172088.1	n.19G>C		non_coding_transcript_exon_variant	Exon 1 of 8
SNTB2	NR_172089.1	n.19G>C		non_coding_transcript_exon_variant	Exon 1 of 7
SNTB2	NR_172090.1	n.19G>C		non_coding_transcript_exon_variant	Exon 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNTB2	ENST00000336278.9	c.16G>C	p.Ala6Pro	missense_variant	Exon 1 of 7	1	NM_006750.4	ENSP00000338191.4
SNTB2	ENST00000467311.5	n.16G>C		non_coding_transcript_exon_variant	Exon 1 of 6	1		ENSP00000436443.1
UTP4	ENST00000567287.2	n.82+19997G>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.16G>C (p.A6P) alteration is located in exon 1 (coding exon 1) of the SNTB2 gene. This alteration results from a G to C substitution at nucleotide position 16, causing the alanine (A) at amino acid position 6 to be replaced by a proline (P). 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	0.17
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.098
Eigen_PC	Benign	-0.0078
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.12
Sift	Benign	0.28	T
Sift4G	Benign	0.24	T
Polyphen		0.64	P
Vest4		0.19
MutPred		0.43		Loss of helix (P = 3e-04);
MVP		0.76
MPC		1.9
ClinPred		0.42	T
GERP RS		3.7
Varity_R		0.26
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-69221085;