NM_001385641.1:c.606G>T

Variant names:

• chr1-926010-G-T
• rs889842126
• NM_001385641.1:c.606G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001385641.1(SAMD11):​c.606G>T​(p.Pro202Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SAMD11 NM_001385641.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.00
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-926010-G-T is Benign according to our data. Variant chr1-926010-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1632958.Status of the report is criteria_provided_single_submitter, 1 stars.

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.606G>T	p.Pro202Pro	synonymous	Exon 2 of 14	NP_001372570.1	A0A087WU74
	SAMD11	NM_001385640.1		c.606G>T	p.Pro202Pro	synonymous	Exon 2 of 14	NP_001372569.1	A0A087WX24
	SAMD11	NM_152486.4		c.69G>T	p.Pro23Pro	synonymous	Exon 2 of 14	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.606G>T	p.Pro202Pro	synonymous	Exon 2 of 14	ENSP00000478421.2	A0A087WU74
	SAMD11	ENST00000968543.1		c.606G>T	p.Pro202Pro	synonymous	Exon 2 of 14	ENSP00000638602.1
	SAMD11	ENST00000618323.5	TSL:5	c.606G>T	p.Pro202Pro	synonymous	Exon 2 of 14	ENSP00000480678.2	A0A087WX24

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248858 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459030 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725898

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.0000197 AC: 1 AN: 50772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111856

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.7
DANN	Benign	0.82
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.44		Position offset: -2

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

Other links and lift over

dbSNP: rs889842126; hg19: chr1-861390;