chr7-93101327-CTT-C

Variant names:

• chr7-93101327-CTT-C
• rs1455031791
• NM_017654.4:c.4769_4770delAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM2 PM4 BP6_Moderate

The NM_017654.4(SAMD9):​c.4769_4770delAA​(p.Ter1590fs) variant causes a frameshift, stop lost change. The variant allele was found at a frequency of 0.00000206 in 1,457,322 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SAMD9 NM_017654.4 frameshift, stop_lost
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.87
• Publications: 0 publications found

Genes affected

SAMD9 (HGNC:1348): (sterile alpha motif domain containing 9) This gene encodes a sterile alpha motif domain-containing protein. The encoded protein localizes to the cytoplasm and may play a role in regulating cell proliferation and apoptosis. Mutations in this gene are the cause of normophosphatemic familial tumoral calcinosis. Alternate splicing results in multiple transcript variants that encode the same protein.[provided by RefSeq, Jul 2010]

SAMD9 Gene-Disease associations (from GenCC):

• MIRAGE syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Orphanet, Ambry Genetics
• SAMD9-related spectrum and myeloid neoplasm risk

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• normophosphatemic familial tumoral calcinosis

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, Genomics England PanelApp, Ambry Genetics, ClinGen
• monosomy 7 myelodysplasia and leukemia syndrome 2

  Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_017654.4 Downstream stopcodon found after 8 codons.
• BP6: Variant 7-93101327-CTT-C is Benign according to our data. Variant chr7-93101327-CTT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2027542.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017654.4. 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
	SAMD9	NM_017654.4	MANE Select	c.4769_4770delAA	p.Ter1590fs	frameshift stop_lost	Exon 3 of 3	NP_060124.2
	SAMD9	NM_001193307.2		c.4769_4770delAA	p.Ter1590fs	frameshift stop_lost	Exon 2 of 2	NP_001180236.1	Q5K651

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD9	ENST00000379958.3	TSL:1 MANE Select	c.4769_4770delAA	p.Ter1590fs	frameshift stop_lost	Exon 3 of 3	ENSP00000369292.2	Q5K651
	SAMD9	ENST00000620985.4	TSL:2	c.4769_4770delAA	p.Ter1590fs	frameshift stop_lost	Exon 2 of 2	ENSP00000484636.1	Q5K651

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457322 Hom.: 0 AF XY: 0.00000138 AC XY: 1 AN XY: 725168

African (AFR) AF: 0.0000598 AC: 2 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110642

Other (OTH) AF: 0.0000166 AC: 1 AN: 60328

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9

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: rs1455031791; hg19: chr7-92730640;