1-930081-AGCCCCACCTTCCTCTCCTCCTGCCCCACCTTCCTCTCCTCCT-AGCCCCACCTTCCTCTCCTCCT

Variant names:

• chr1-930081-AGCCCCACCTTCCTCTCCTCCT-A
• rs879326979
• NM_001385641.1:c.610-23_610-3delTTCCTCTCCTCCTGCCCCACC

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS2

The NM_001385641.1(SAMD11):​c.610-23_610-3delTTCCTCTCCTCCTGCCCCACC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000889 in 1,475,018 control chromosomes in the GnomAD database, including 4 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00074 (3 hom.)
• Consequence: SAMD11 NM_001385641.1 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.35
• Publications: 0 publications found

Genes affected

SAMD11 (HGNC:28706): (sterile alpha motif domain containing 11) Predicted to enable several functions, including histone binding activity; protein domain specific binding activity; and protein self-association. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SAMD11 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Franklin by Genoox

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP6: Variant 1-930081-AGCCCCACCTTCCTCTCCTCCT-A is Benign according to our data. Variant chr1-930081-AGCCCCACCTTCCTCTCCTCCT-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3038970.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385641.1. 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
	SAMD11	NM_001385641.1	MANE Select	c.610-23_610-3delTTCCTCTCCTCCTGCCCCACC		splice_region intron	N/A	NP_001372570.1	A0A087WU74
	SAMD11	NM_001385640.1		c.610-23_610-3delTTCCTCTCCTCCTGCCCCACC		splice_region intron	N/A	NP_001372569.1	A0A087WX24
	SAMD11	NM_152486.4		c.73-23_73-3delTTCCTCTCCTCCTGCCCCACC		splice_region intron	N/A	NP_689699.3	Q96NU1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD11	ENST00000616016.5	TSL:5 MANE Select	c.610-73_610-53delGCCCCACCTTCCTCTCCTCCT		intron	N/A	ENSP00000478421.2	A0A087WU74
	SAMD11	ENST00000968543.1		c.610-73_610-53delGCCCCACCTTCCTCTCCTCCT		intron	N/A	ENSP00000638602.1
	SAMD11	ENST00000618323.5	TSL:5	c.610-73_610-53delGCCCCACCTTCCTCTCCTCCT		intron	N/A	ENSP00000480678.2	A0A087WX24

Frequencies

GnomAD3 genomes AF: 0.00219 AC: 332 AN: 151426 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00581

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00233

Gnomad SAS AF: 0.00147

Gnomad FIN AF: 0.00142

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000590

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000737 AC: 975 AN: 1323474 Hom.: 3 AF XY: 0.000789 AC XY: 511 AN XY: 647992

African (AFR) AF: 0.00334 AC: 101 AN: 30198

American (AMR) AF: 0.000618 AC: 20 AN: 32362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21666

East Asian (EAS) AF: 0.00588 AC: 205 AN: 34864

South Asian (SAS) AF: 0.000706 AC: 49 AN: 69428

European-Finnish (FIN) AF: 0.00261 AC: 120 AN: 45972

Middle Eastern (MID) AF: 0.000258 AC: 1 AN: 3876

European-Non Finnish (NFE) AF: 0.000411 AC: 423 AN: 1030176

Other (OTH) AF: 0.00102 AC: 56 AN: 54932

GnomAD4 genome AF: 0.00222 AC: 337 AN: 151544 Hom.: 1 Cov.: 33 AF XY: 0.00209 AC XY: 155 AN XY: 74028

African (AFR) AF: 0.00591 AC: 244 AN: 41276

American (AMR) AF: 0.00125 AC: 19 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00234 AC: 12 AN: 5132

South Asian (SAS) AF: 0.00147 AC: 7 AN: 4766

European-Finnish (FIN) AF: 0.00142 AC: 15 AN: 10564

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

European-Non Finnish (NFE) AF: 0.000590 AC: 40 AN: 67806

Other (OTH) AF: 0.00 AC: 0 AN: 2100

Alfa AF: 0.00153 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SAMD11-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs879326979; hg19: chr1-865461;