6-100420844-GG-CC

Variant names:

• chr6-100420844-GG-CC
• NM_005068.3:c.1112_1113delCCinsGG
• SIM1 p.Ala371Gly

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005068.3(SIM1):​c.1112_1113delCCinsGG​(p.Ala371Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A371V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIM1 NM_005068.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIM1	NM_005068.3	MANE Select	c.1112_1113delCCinsGG	p.Ala371Gly	missense	N/A	NP_005059.2
	SIM1	NM_001374769.1		c.1112_1113delCCinsGG	p.Ala371Gly	missense	N/A	NP_001361698.1	P81133
	SIM1-AS1	NR_187148.1		n.891-6274_891-6273delGGinsCC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIM1	ENST00000369208.8	TSL:1 MANE Select	c.1112_1113delCCinsGG	p.Ala371Gly	missense	N/A	ENSP00000358210.4	P81133
	SIM1	ENST00000262901.4	TSL:1	c.1112_1113delCCinsGG	p.Ala371Gly	missense	N/A	ENSP00000262901.4	P81133
	SIM1	ENST00000900753.1		c.1112_1113delCCinsGG	p.Ala371Gly	missense	N/A	ENSP00000570812.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1

Splicing

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.

Other links and lift over

hg19: chr6-100868720;