NM_001290403.2:c.925G>T

Variant names:

• chr1-47219791-C-A
• rs143072042
• NM_001290403.2:c.925G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001290403.2(TAL1):​c.925G>T​(p.Ala309Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000473 in 1,611,664 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (1 hom.)
• Consequence: TAL1 NM_001290403.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31
• Publications: 2 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.036818624).
• BS2: High AC in GnomAd4 at 41 AD gene.

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.925G>T	p.Ala309Ser	missense	Exon 5 of 5	NP_001277332.1	P17542-1
	TAL1	NM_001287347.2		c.925G>T	p.Ala309Ser	missense	Exon 5 of 5	NP_001274276.1	Q16509
	TAL1	NM_001290404.1		c.925G>T	p.Ala309Ser	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.925G>T	p.Ala309Ser	missense	Exon 5 of 5	ENSP00000510655.1	P17542-1
	TAL1	ENST00000294339.3	TSL:1	c.925G>T	p.Ala309Ser	missense	Exon 4 of 4	ENSP00000294339.3	P17542-1
	TAL1	ENST00000371884.6	TSL:1	c.925G>T	p.Ala309Ser	missense	Exon 5 of 5	ENSP00000360951.1	P17542-1

Frequencies

GnomAD3 genomes AF: 0.000269 AC: 41 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000411 AC: 100 AN: 243590 AF XY: 0.000390

Gnomad AFR exome AF: 0.000198

Gnomad AMR exome AF: 0.000175

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000488

Gnomad NFE exome AF: 0.000576

Gnomad OTH exome AF: 0.000669

GnomAD4 exome AF: 0.000494 AC: 721 AN: 1459472 Hom.: 1 Cov.: 29 AF XY: 0.000475 AC XY: 345 AN XY: 726096

African (AFR) AF: 0.0000896 AC: 3 AN: 33466

American (AMR) AF: 0.000179 AC: 8 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26078

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.000534 AC: 46 AN: 86166

European-Finnish (FIN) AF: 0.000620 AC: 32 AN: 51616

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.000541 AC: 601 AN: 1111666

Other (OTH) AF: 0.000464 AC: 28 AN: 60350

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22 AN XY: 74344

African (AFR) AF: 0.0000241 AC: 1 AN: 41442

American (AMR) AF: 0.000327 AC: 5 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4836

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68040

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.0000718 Hom.: 0

Bravo AF: 0.000249

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.000466 AC: 4

ExAC AF: 0.000413 AC: 50

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.71	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.037	T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.3
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.25
Sift	Benign	0.78	T
Sift4G	Benign	0.17	T
Polyphen		0.049	B
Vest4		0.066
MVP		0.64
MPC		0.62
ClinPred		0.0064	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.048
gMVP		0.15
Mutation Taster		=94/6	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: rs143072042; hg19: chr1-47685463; COSMIC: COSV104539531;