8-50402258-A-C

Variant names:

• chr8-50402258-A-C
• rs35384568
• NM_018967.5:c.76A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_018967.5(SNTG1):​c.76A>C​(p.Lys26Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000319 in 1,613,276 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: SNTG1 NM_018967.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 6.53
• Publications: 3 publications found

Genes affected

SNTG1 (HGNC:13740): (syntrophin gamma 1) The protein encoded by this gene is a member of the syntrophin family. Syntrophins are cytoplasmic peripheral membrane proteins that typically contain 2 pleckstrin homology (PH) domains, a PDZ domain that bisects the first PH domain, and a C-terminal domain that mediates dystrophin binding. This family member plays a role in mediating gamma-enolase trafficking to the plasma membrane and in enhancing its neurotrophic activity. Mutations in this gene are associated with idiopathic scoliosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0095977485).
• BP6: Variant 8-50402258-A-C is Benign according to our data. Variant chr8-50402258-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 728154.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018967.5. 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
	SNTG1	NM_018967.5	MANE Select	c.76A>C	p.Lys26Gln	missense	Exon 4 of 19	NP_061840.1	Q9NSN8-1
	SNTG1	NM_001287813.3		c.76A>C	p.Lys26Gln	missense	Exon 5 of 20	NP_001274742.1	Q9NSN8-1
	SNTG1	NM_001321773.2		c.76A>C	p.Lys26Gln	missense	Exon 3 of 18	NP_001308702.1	Q9NSN8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNTG1	ENST00000642720.2	MANE Select	c.76A>C	p.Lys26Gln	missense	Exon 4 of 19	ENSP00000493900.1	Q9NSN8-1
	SNTG1	ENST00000518864.5	TSL:1	c.76A>C	p.Lys26Gln	missense	Exon 5 of 20	ENSP00000429276.1	Q9NSN8-1
	SNTG1	ENST00000517473.5	TSL:1	c.76A>C	p.Lys26Gln	missense	Exon 3 of 17	ENSP00000431123.1	Q9NSN8-2

Frequencies

GnomAD3 genomes AF: 0.00172 AC: 261 AN: 152168 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00512

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000459 AC: 115 AN: 250530 AF XY: 0.000295

Gnomad AFR exome AF: 0.00560

Gnomad AMR exome AF: 0.000552

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.000654

GnomAD4 exome AF: 0.000173 AC: 253 AN: 1460990 Hom.: 1 Cov.: 33 AF XY: 0.000138 AC XY: 100 AN XY: 726774

African (AFR) AF: 0.00500 AC: 167 AN: 33394

American (AMR) AF: 0.000719 AC: 32 AN: 44504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111804

Other (OTH) AF: 0.000596 AC: 36 AN: 60360

GnomAD4 genome AF: 0.00171 AC: 261 AN: 152286 Hom.: 1 Cov.: 32 AF XY: 0.00173 AC XY: 129 AN XY: 74470

African (AFR) AF: 0.00510 AC: 212 AN: 41560

American (AMR) AF: 0.00294 AC: 45 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.000755 Hom.: 0

Bravo AF: 0.00229

ESP6500AA AF: 0.00431 AC: 19

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000494 AC: 60

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	SNTG1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.017	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.0096	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.5
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.13
Sift	Benign	0.35	T
Sift4G	Benign	0.53	T
Polyphen		0.76	P
Vest4		0.50
MVP		0.61
MPC		0.065
ClinPred		0.046	T
GERP RS		5.0
Varity_R		0.24
gMVP		0.29
Mutation Taster		=81/19	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: rs35384568; hg19: chr8-51314818;