7-75109010-T-C

Variant names:

• chr7-75109010-T-C
• NM_001003795.3:c.46T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001003795.3(GTF2IRD2B):​c.46T>C​(p.Ser16Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 11)
• Consequence: GTF2IRD2B NM_001003795.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.441

Genes affected

GTF2IRD2B (HGNC:33125): (GTF2I repeat domain containing 2B) This gene encodes a glycosylated phosphoprotein with a leucine zipper motif, two helix-loop-helix motifs (I repeats) that are similar to domains found in the TFII-I family of transcription factors, one CHARLIE8 transposable element-like sequence, and a BED zinc finger. This gene lies within a region that is deleted in Williams-Beuren syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08541009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2IRD2B	NM_001003795.3	c.46T>C	p.Ser16Pro	missense_variant	Exon 2 of 16	ENST00000472837.7	NP_001003795.1
GTF2IRD2B	NM_001368302.1	c.532T>C	p.Ser178Pro	missense_variant	Exon 2 of 16		NP_001355231.1
GTF2IRD2B	NM_001368301.1	c.46T>C	p.Ser16Pro	missense_variant	Exon 2 of 3		NP_001355230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2IRD2B	ENST00000472837.7	c.46T>C	p.Ser16Pro	missense_variant	Exon 2 of 16	1	NM_001003795.3	ENSP00000480524.1

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD4 exome Cov.: 10

GnomAD4 genome Cov.: 11

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.46T>C (p.S16P) alteration is located in exon 2 (coding exon 1) of the GTF2IRD2B gene. This alteration results from a T to C substitution at nucleotide position 46, causing the serine (S) at amino acid position 16 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.017	T;.;.;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.75	T;.;T;.
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.085	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;.;.
PrimateAI	Uncertain	0.52	T
Sift4G	Benign	0.066	T;T;T;T
Polyphen		0.0040	B;.;.;.
Vest4		0.19
MutPred		0.21		Loss of phosphorylation at S16 (P = 0.0215);Loss of phosphorylation at S16 (P = 0.0215);Loss of phosphorylation at S16 (P = 0.0215);Loss of phosphorylation at S16 (P = 0.0215);
MVP		0.014
ClinPred		0.071	T
GERP RS		0.11
Varity_R		0.13
gMVP		0.069

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-74524802;