1-23559007-T-A

Position:

• chr1-23559007-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000374561.6(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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T105A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ID3 ENST00000374561.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496

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]

LOC124903876 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ID3	NM_002167.5	c.313A>T	p.Thr105Ser	missense_variant	2/3	ENST00000374561.6	NP_002158.3
LOC124903876	XR_007065537.1	n.282+6912T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ID3	ENST00000374561.6	c.313A>T	p.Thr105Ser	missense_variant	2/3	1	NM_002167.5	ENSP00000363689	P1
ID3	ENST00000486541.1	n.330A>T		non_coding_transcript_exon_variant	2/2	1
ID3	ENST00000463312.1	n.69A>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	P
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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs11574; hg19: chr1-23885498;