Genetic Variant SIM1:c.1167+10797C>T (chr6-100409993-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005068.3(SIM1):c.1167+10797C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,050 control chromosomes in the GnomAD database, including 5,985 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 0.27 ( 5985 hom., cov: 32)

Consequence

SIM1
NM_005068.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.755

Publications

2 publications found

Variant links:

Genes affected

SIM1 (HGNC:10882): (SIM bHLH transcription factor 1) SIM1 and SIM2 genes are Drosophila single-minded (sim) gene homologs. SIM1 transcript was detected only in fetal kidney out of various adult and fetal tissues tested. Since the sim gene plays an important role in Drosophila development and has peak levels of expression during the period of neurogenesis,it was proposed that the human SIM gene is a candidate for involvement in certain dysmorphic features (particularly the facial and skull characteristics), abnormalities of brain development, and/or cognitive disability of Down syndrome. [provided by RefSeq, Jul 2008]

SIM1 links:

SIM1-AS1 (HGNC:40530): (SIM1 antisense RNA 1)

SIM1-AS1 links:

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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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005068.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SIM1	NM_005068.3	MANE Select	c.1167+10797C>T	intron	N/A	NP_005059.2
SIM1	NM_001374769.1		c.1167+10797C>T	intron	N/A	NP_001361698.1	P81133
SIM1-AS1	NR_187148.1		n.890+15618G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SIM1	ENST00000369208.8	TSL:1 MANE Select	c.1167+10797C>T	intron	N/A	ENSP00000358210.4	P81133
SIM1	ENST00000262901.4	TSL:1	c.1167+10797C>T	intron	N/A	ENSP00000262901.4	P81133
SIM1	ENST00000900753.1		c.1167+10797C>T	intron	N/A	ENSP00000570812.1

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41188

AN:

151932

Hom.:

5965

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.573

Gnomad SAS

AF:

0.260

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.262

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.271

AC:

41240

AN:

152050

Hom.:

5985

Cov.:

AF XY:

0.274

AC XY:

20388

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.195

AC:

8075

AN:

41492

American (AMR)

AF:

0.338

AC:

5154

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

888

AN:

3472

East Asian (EAS)

AF:

0.574

AC:

2960

AN:

5160

South Asian (SAS)

AF:

0.260

AC:

1251

AN:

4816

European-Finnish (FIN)

AF:

0.292

AC:

3088

AN:

10562

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.279

AC:

18985

AN:

67962

Other (OTH)

AF:

0.272

AC:

575

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1510

3021

4531

6042

7552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<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:

0.276

Hom.:

7520

Bravo

AF:

0.273

Asia WGS

AF:

0.400

AC:

1386

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.5

(source)

DANN

Benign

0.84

PhyloP100

-0.76

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

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