Genetic Variant SGMS1:c.624-7565A>G (chr10-50334887-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_147156.4(SGMS1):c.624-7565A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,158 control chromosomes in the GnomAD database, including 4,682 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4673 hom., cov: 32)

Exomes 𝑓: 0.29 ( 9 hom. )

Consequence

SGMS1
NM_147156.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.36

Publications

2 publications found

Variant links:

Genes affected

SGMS1 (HGNC:29799): (sphingomyelin synthase 1) The protein encoded by this gene is predicted to be a five-pass transmembrane protein. This gene may be predominately expressed in brain. [provided by RefSeq, Jul 2008]

SGMS1 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

SGMS1 links:

ENSG00000279863 (HGNC:):

ENSG00000279863 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_147156.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147156.4. 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
	SGMS1	NM_147156.4	MANE Select	c.624-7565A>G		intron	N/A	NP_671512.1	Q86VZ5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SGMS1	ENST00000361781.7	TSL:1 MANE Select	c.624-7565A>G	intron	N/A	ENSP00000354829.2	Q86VZ5-1
SGMS1	ENST00000361543.3	TSL:1	c.*193+5500A>G	intron	N/A	ENSP00000355235.2	C0MHM2
SGMS1	ENST00000626236.2	TSL:1	n.*110+5500A>G	intron	N/A	ENSP00000486310.1	C0MHM2

Frequencies

GnomAD3 genomes

AF:

0.227

AC:

34522

AN:

151902

Hom.:

4660

Cov.:

show subpopulations

Gnomad AFR

AF:

0.213

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.174

Gnomad EAS

AF:

0.633

Gnomad SAS

AF:

0.493

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.210

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.239

GnomAD4 exome

AF:

0.290

AC:

AN:

138

Hom.:

Cov.:

AF XY:

0.269

AC XY:

AN XY:

104

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.750

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.204

AC:

AN:

108

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.541

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.227

AC:

34565

AN:

152020

Hom.:

4673

Cov.:

AF XY:

0.236

AC XY:

17562

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.213

AC:

8832

AN:

41466

American (AMR)

AF:

0.284

AC:

4340

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

604

AN:

3468

East Asian (EAS)

AF:

0.633

AC:

3268

AN:

5166

South Asian (SAS)

AF:

0.493

AC:

2365

AN:

4800

European-Finnish (FIN)

AF:

0.183

AC:

1933

AN:

10578

Middle Eastern (MID)

AF:

0.202

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.185

AC:

12549

AN:

67946

Other (OTH)

AF:

0.243

AC:

513

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1276

2553

3829

5106

6382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

374

748

1122

1496

1870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.197

Hom.:

2054

Bravo

AF:

0.232

Asia WGS

AF:

0.529

AC:

1841

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.13

(source)

DANN

Benign

0.63

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over