rs768781633

Variant names:

• chr18-3447765-C-G
• rs768781633
• NM_173207.4:c.26C>G

Your query was ambiguous. Multiple possible variants found:

• chr18-3447765-C-G
• chr18-3447765-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173207.4(TGIF1):​c.26C>G​(p.Ala9Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TGIF1 NM_173207.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242

Genes affected

TGIF1 (HGNC:11776): (TGFB induced factor homeobox 1) The protein encoded by this gene is a member of the three-amino acid loop extension (TALE) superclass of atypical homeodomains. TALE homeobox proteins are highly conserved transcription regulators. This particular homeodomain binds to a previously characterized retinoid X receptor responsive element from the cellular retinol-binding protein II promoter. In addition to its role in inhibiting 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element, the protein is an active transcriptional co-repressor of SMAD2 and may participate in the transmission of nuclear signals during development and in the adult. Mutations in this gene are associated with holoprosencephaly type 4, which is a structural anomaly of the brain. Alternative splicing has been observed at this locus and multiple splice variants encoding distinct isoforms are described. [provided by RefSeq, Jul 2013]

LOC124904237 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.067536116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGIF1	NM_173207.4	c.26C>G	p.Ala9Gly	missense_variant	Exon 1 of 3		NP_775299.1
TGIF1	NM_001278686.3	c.-44-8589C>G		intron_variant	Intron 2 of 3		NP_001265615.1
TGIF1	NM_174886.3	c.-44-8589C>G		intron_variant	Intron 2 of 3		NP_777480.1
LOC124904237	XR_007066269.1	n.126-579G>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGIF1	ENST00000618001.4	c.26C>G	p.Ala9Gly	missense_variant	Exon 1 of 3	2		ENSP00000483499.1
TGIF1	ENST00000401449.5	c.-44-8589C>G		intron_variant	Intron 2 of 3	2		ENSP00000385206.1
TGIF1	ENST00000548489.6	c.-44-8589C>G		intron_variant	Intron 2 of 3	3		ENSP00000447747.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.0
DANN	Benign	0.87
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.0	T
Sift4G	Benign	0.19	T
Vest4		0.21
MVP		0.15
ClinPred		0.16	T
GERP RS		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs768781633; hg19: chr18-3447763;