rs777427139

Variant names:

• chr1-47219911-C-A
• rs777427139
• NM_001290403.2:c.805G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-47219911-C-A
• chr1-47219911-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001290403.2(TAL1):​c.805G>T​(p.Gly269Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000744 in 1,344,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G269S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: TAL1 NM_001290403.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.851
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1933097).

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.805G>T	p.Gly269Cys	missense	Exon 5 of 5	NP_001277332.1	P17542-1
	TAL1	NM_001287347.2		c.805G>T	p.Gly269Cys	missense	Exon 5 of 5	NP_001274276.1	Q16509
	TAL1	NM_001290404.1		c.805G>T	p.Gly269Cys	missense	Exon 6 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.805G>T	p.Gly269Cys	missense	Exon 5 of 5	ENSP00000510655.1	P17542-1
	TAL1	ENST00000294339.3	TSL:1	c.805G>T	p.Gly269Cys	missense	Exon 4 of 4	ENSP00000294339.3	P17542-1
	TAL1	ENST00000371884.6	TSL:1	c.805G>T	p.Gly269Cys	missense	Exon 5 of 5	ENSP00000360951.1	P17542-1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.44e-7 AC: 1 AN: 1344700 Hom.: 0 Cov.: 65 AF XY: 0.00000152 AC XY: 1 AN XY: 658078

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31032

American (AMR) AF: 0.00 AC: 0 AN: 33266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21274

East Asian (EAS) AF: 0.0000270 AC: 1 AN: 37014

South Asian (SAS) AF: 0.00 AC: 0 AN: 71390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3728

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1045518

Other (OTH) AF: 0.00 AC: 0 AN: 55444

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.67	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.85
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.88	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.048	D
Polyphen		0.62	P
Vest4		0.34
MutPred		0.37		Loss of loop (P = 0.3664)
MVP		0.65
MPC		1.3
ClinPred		0.34	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.35
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs777427139; hg19: chr1-47685583;