chr2-27149221-G-T

Variant names:

• chr2-27149221-G-T
• rs775507415
• NM_175769.3:c.88G>T

Variant summary

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

The NM_175769.3(TCF23):​c.88G>T​(p.Ala30Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,440 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A30T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TCF23 NM_175769.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574
• Publications: 0 publications found

Genes affected

TCF23 (HGNC:18602): (transcription factor 23) The gene encodes a member of the basic helix-loop-helix transcription factor family. Studies of the orthologous gene in mouse have shown the encoded protein does not bind DNA but may negatively regulate other basic helix-loop-helix factors via the formation of a functionally inactive heterodimeric complex. [provided by RefSeq, May 2010]

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=0.035272866).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175769.3. 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
	TCF23	NM_175769.3	MANE Select	c.88G>T	p.Ala30Ser	missense	Exon 1 of 3	NP_786951.1	Q7RTU1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF23	ENST00000296096.6	TSL:1 MANE Select	c.88G>T	p.Ala30Ser	missense	Exon 1 of 3	ENSP00000296096.5	Q7RTU1
	TCF23	ENST00000968520.1		c.88G>T	p.Ala30Ser	missense	Exon 1 of 2	ENSP00000638579.1
	TCF23	ENST00000407815.3	TSL:4	n.197G>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1408440 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 695494

African (AFR) AF: 0.00 AC: 0 AN: 32094

American (AMR) AF: 0.00 AC: 0 AN: 36552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25240

East Asian (EAS) AF: 0.00 AC: 0 AN: 36658

South Asian (SAS) AF: 0.00 AC: 0 AN: 79746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5472

European-Non Finnish (NFE) AF: 9.22e-7 AC: 1 AN: 1084392

Other (OTH) AF: 0.00 AC: 0 AN: 58394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	0.10
DANN	Benign	0.96
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.035	T
MetaSVM	Uncertain	0.050	D
MutationAssessor	Benign	0.34	N
PhyloP100		-0.57
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.27
Sift	Uncertain	0.021	D
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.051
MutPred		0.17		Gain of phosphorylation at A30 (P = 0.0073)
MVP		0.16
MPC		0.34
ClinPred		0.16	T
GERP RS		1.8
PromoterAI		-0.018	Neutral
Varity_R		0.037
gMVP		0.22
Mutation Taster		=95/5	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: rs775507415; hg19: chr2-27372089;