1-23559007-T-A

Variant names:

• chr1-23559007-T-A
• rs11574
• NM_002167.5:c.313A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002167.5(ID3):​c.313A>T​(p.Thr105Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ID3 NM_002167.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496
• Publications: 66 publications found

Genes affected

ID3 (HGNC:5362): (inhibitor of DNA binding 3) The protein encoded by this gene is a helix-loop-helix (HLH) protein that can form heterodimers with other HLH proteins. However, the encoded protein lacks a basic DNA-binding domain and therefore inhibits the DNA binding of any HLH protein with which it interacts. [provided by RefSeq, Aug 2011]

ENSG00000307540 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027305275).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002167.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ID3	NM_002167.5	MANE Select	c.313A>T	p.Thr105Ser	missense	Exon 2 of 3	NP_002158.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ID3	ENST00000374561.6	TSL:1 MANE Select	c.313A>T	p.Thr105Ser	missense	Exon 2 of 3	ENSP00000363689.5
	ID3	ENST00000486541.1	TSL:1	n.330A>T		non_coding_transcript_exon	Exon 2 of 2
	ID3	ENST00000463312.1	TSL:2	n.69A>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 114951

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.10
DANN	Benign	0.71
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.027	N
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.50
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.59	N
REVEL	Benign	0.039
Sift	Benign	0.99	T
Sift4G	Benign	0.83	T
Polyphen		0.010	B
Vest4		0.090
MutPred		0.16		Gain of disorder (P = 0.0398)
MVP		0.19
MPC		0.11
ClinPred		0.041	T
GERP RS		-2.8
PromoterAI		-0.049	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.22
Mutation Taster		=96/4	polymorphism

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: rs11574; hg19: chr1-23885498;