7-75112464-T-C

Variant names:

• chr7-75112464-T-C
• NM_001003795.3:c.167T>C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001003795.3(GTF2IRD2B):​c.167T>C​(p.Val56Ala) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 7)
• Consequence: GTF2IRD2B NM_001003795.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.23

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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30291498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2IRD2B	NM_001003795.3	c.167T>C	p.Val56Ala	missense_variant	Exon 3 of 16	ENST00000472837.7	NP_001003795.1
GTF2IRD2B	NM_001368302.1	c.653T>C	p.Val218Ala	missense_variant	Exon 3 of 16		NP_001355231.1
GTF2IRD2B	NM_001368301.1	c.167T>C	p.Val56Ala	missense_variant	Exon 3 of 3		NP_001355230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2IRD2B	ENST00000472837.7	c.167T>C	p.Val56Ala	missense_variant	Exon 3 of 16	1	NM_001003795.3	ENSP00000480524.1

Frequencies

GnomAD3 genomes Cov.: 7

GnomAD4 exome Cov.: 8

GnomAD4 genome Cov.: 7

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.167T>C (p.V56A) alteration is located in exon 3 (coding exon 2) of the GTF2IRD2B gene. This alteration results from a T to C substitution at nucleotide position 167, causing the valine (V) at amino acid position 56 to be replaced by an alanine (A). 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	Uncertain	0.47
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T;.;.;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.83	T;.;T;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.5	M;.;.;.
PrimateAI	Uncertain	0.79	T
Sift4G	Uncertain	0.033	D;D;D;D
Polyphen		0.99	D;.;.;.
Vest4		0.48
MutPred		0.27		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.048
ClinPred		0.95	D
GERP RS		3.2
Varity_R		0.24
gMVP		0.11

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: chr7-74528258;