chr1-47225494-G-T

Variant names:

• chr1-47225494-G-T
• rs886951676
• NM_001290403.2:c.395C>A

Variant summary

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

The NM_001290403.2(TAL1):​c.395C>A​(p.Pro132His) variant causes a missense change. The variant allele was found at a frequency of 0.000000923 in 1,083,248 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P132R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: TAL1 NM_001290403.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.62
• Publications: 0 publications found

Genes affected

TAL1 (HGNC:11556): (TAL bHLH transcription factor 1, erythroid differentiation factor) Enables several functions, including DNA-binding transcription factor activity; E-box binding activity; and histone deacetylase binding activity. Involved in several processes, including myeloid cell differentiation; positive regulation of cellular component organization; and positive regulation of erythrocyte differentiation. Located in chromatin and nucleoplasm. Part of transcription regulator complex. Implicated in acute lymphoblastic leukemia. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290403.2. 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
	TAL1	NM_001290403.2	MANE Select	c.395C>A	p.Pro132His	missense	Exon 3 of 5	NP_001277332.1	P17542-1
	TAL1	NM_001287347.2		c.395C>A	p.Pro132His	missense	Exon 3 of 5	NP_001274276.1	Q16509
	TAL1	NM_001290404.1		c.395C>A	p.Pro132His	missense	Exon 4 of 6	NP_001277333.1	P17542-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAL1	ENST00000691006.1	MANE Select	c.395C>A	p.Pro132His	missense	Exon 3 of 5	ENSP00000510655.1	P17542-1
	TAL1	ENST00000294339.3	TSL:1	c.395C>A	p.Pro132His	missense	Exon 2 of 4	ENSP00000294339.3	P17542-1
	TAL1	ENST00000371884.6	TSL:1	c.395C>A	p.Pro132His	missense	Exon 3 of 5	ENSP00000360951.1	P17542-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.23e-7 AC: 1 AN: 1083248 Hom.: 0 Cov.: 33 AF XY: 0.00000195 AC XY: 1 AN XY: 512210

African (AFR) AF: 0.00 AC: 0 AN: 22852

American (AMR) AF: 0.00 AC: 0 AN: 8344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14314

East Asian (EAS) AF: 0.00 AC: 0 AN: 26464

South Asian (SAS) AF: 0.00 AC: 0 AN: 19868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2924

European-Non Finnish (NFE) AF: 0.00000108 AC: 1 AN: 923480

Other (OTH) AF: 0.00 AC: 0 AN: 43778

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.44	T
M_CAP	Pathogenic	0.91	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Pathogenic	0.90	D
MutationAssessor	Benign	1.6	L
PhyloP100		3.6
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.40
Sift	Benign	0.056	T
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.23
MutPred		0.34		Loss of relative solvent accessibility (P = 0.0071)
MVP		0.70
MPC		1.4
ClinPred		0.98	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.26
gMVP		0.59
Mutation Taster		=89/11	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: rs886951676; hg19: chr1-47691166;