NM_003202.5:c.369C>T

Variant names:

• chr5-134115961-C-T
• rs149417339
• NM_003202.5:c.369C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_003202.5(TCF7):​c.369C>T​(p.Ser123Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 1,614,032 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0035 (8 hom.)
• Consequence: TCF7 NM_003202.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.02
• Publications: 0 publications found

Genes affected

TCF7 (HGNC:11639): (transcription factor 7) This gene encodes a member of the T-cell factor/lymphoid enhancer-binding factor family of high mobility group (HMG) box transcriptional activators. This gene is expressed predominantly in T-cells and plays a critical role in natural killer cell and innate lymphoid cell development. The encoded protein forms a complex with beta-catenin and activates transcription through a Wnt/beta-catenin signaling pathway. Mice with a knockout of this gene are viable and fertile, but display a block in T-lymphocyte differentiation. Alternative splicing results in multiple transcript variants. Naturally-occurring isoforms lacking the N-terminal beta-catenin interaction domain may act as dominant negative regulators of Wnt signaling. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 5-134115961-C-T is Benign according to our data. Variant chr5-134115961-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2655705.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.02 with no splicing effect.
• BS2: High AC in GnomAd4 at 380 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003202.5. 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
	TCF7	NM_003202.5	MANE Select	c.369C>T	p.Ser123Ser	synonymous	Exon 3 of 10	NP_003193.2
	TCF7	NM_001346425.2		c.369C>T	p.Ser123Ser	synonymous	Exon 3 of 11	NP_001333354.1
	TCF7	NM_001346450.2		c.24C>T	p.Ser8Ser	synonymous	Exon 2 of 10	NP_001333379.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7	ENST00000342854.10	TSL:1 MANE Select	c.369C>T	p.Ser123Ser	synonymous	Exon 3 of 10	ENSP00000340347.5	P36402-5
	TCF7	ENST00000395023.5	TSL:1	c.24C>T	p.Ser8Ser	synonymous	Exon 2 of 9	ENSP00000378469.1	P36402-6
	TCF7	ENST00000518915.5	TSL:1	c.24C>T	p.Ser8Ser	synonymous	Exon 2 of 9	ENSP00000430179.1	P36402-2

Frequencies

GnomAD3 genomes AF: 0.00250 AC: 381 AN: 152248 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00391

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00283 AC: 711 AN: 250848 AF XY: 0.00286

Gnomad AFR exome AF: 0.000556

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00310

Gnomad NFE exome AF: 0.00441

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00351 AC: 5129 AN: 1461666 Hom.: 8 Cov.: 32 AF XY: 0.00345 AC XY: 2507 AN XY: 727116

African (AFR) AF: 0.000448 AC: 15 AN: 33480

American (AMR) AF: 0.00244 AC: 109 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00107 AC: 28 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000904 AC: 78 AN: 86258

European-Finnish (FIN) AF: 0.00302 AC: 161 AN: 53228

Middle Eastern (MID) AF: 0.00399 AC: 23 AN: 5768

European-Non Finnish (NFE) AF: 0.00405 AC: 4508 AN: 1111988

Other (OTH) AF: 0.00343 AC: 207 AN: 60390

GnomAD4 genome AF: 0.00249 AC: 380 AN: 152366 Hom.: 0 Cov.: 33 AF XY: 0.00264 AC XY: 197 AN XY: 74510

African (AFR) AF: 0.000794 AC: 33 AN: 41586

American (AMR) AF: 0.00261 AC: 40 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4834

European-Finnish (FIN) AF: 0.00188 AC: 20 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00390 AC: 265 AN: 68034

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00354 Hom.: 0

Bravo AF: 0.00266

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00349

EpiControl AF: 0.00421

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	8.9
DANN	Benign	0.90
PhyloP100		-1.0
PromoterAI		-0.057	Neutral
Mutation Taster		=100/0	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: rs149417339; hg19: chr5-133451652;