rs2251166

Variant names:

• chr3-9400053-G-A
• rs2251166
• NM_001080517.3:c.-177+2076G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-9400053-G-A
• chr3-9400053-G-C
• chr3-9400053-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001080517.3(SETD5):​c.-177+2076G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,094 control chromosomes in the GnomAD database, including 38,431 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 0.70 (38431 hom., cov: 32)
• Consequence: SETD5 NM_001080517.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285
• Publications: 8 publications found

Genes affected

SETD5 (HGNC:25566): (SET domain containing 5) This function of this gene has yet to be determined but based on sequence similarity to other SET domain proteins it may function as a histone methyltransferase. Mutations in this gene have been associated with an autosomal dominant form of intellectual disability. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2017]

SETD5 Gene-Disease associations (from GenCC):

• intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Orphanet
• syndromic complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080517.3. 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
	SETD5	NM_001080517.3	MANE Select	c.-177+2076G>A		intron	N/A	NP_001073986.1	Q9C0A6-1
	SETD5	NM_001437635.1		c.-177+2076G>A		intron	N/A	NP_001424564.1
	SETD5	NM_001437633.1		c.-177+2076G>A		intron	N/A	NP_001424562.1	A0A804HKJ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETD5	ENST00000402198.7	TSL:5 MANE Select	c.-177+2076G>A		intron	N/A	ENSP00000385852.2	Q9C0A6-1
	SETD5	ENST00000682536.1		c.-177+2076G>A		intron	N/A	ENSP00000507956.1	A0A804HKJ9
	SETD5	ENST00000866906.1		c.-190+2076G>A		intron	N/A	ENSP00000536965.1

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106318 AN: 151976 Hom.: 38439 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.869

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.699 AC: 106329 AN: 152094 Hom.: 38431 Cov.: 32 AF XY: 0.707 AC XY: 52606 AN XY: 74360

African (AFR) AF: 0.504 AC: 20895 AN: 41458

American (AMR) AF: 0.707 AC: 10808 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2763 AN: 3472

East Asian (EAS) AF: 0.878 AC: 4531 AN: 5162

South Asian (SAS) AF: 0.856 AC: 4128 AN: 4820

European-Finnish (FIN) AF: 0.849 AC: 9001 AN: 10596

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51649 AN: 67982

Other (OTH) AF: 0.725 AC: 1528 AN: 2108

Alfa AF: 0.748 Hom.: 22486

Bravo AF: 0.681

Asia WGS AF: 0.798 AC: 2775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.95
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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: rs2251166; hg19: chr3-9441737;