chr7-75123223-C-T

Variant names:

• chr7-75123223-C-T
• rs782783918
• NM_001003795.3:c.446C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001003795.3(GTF2IRD2B):​c.446C>T​(p.Pro149Leu) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000078 (1 hom., cov: 19)
  • Exomes 𝑓: 0.000070 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GTF2IRD2B NM_001003795.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.03
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.932

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003795.3. 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
	GTF2IRD2B	NM_001003795.3	MANE Select	c.446C>T	p.Pro149Leu	missense	Exon 5 of 16	NP_001003795.1	Q6EKJ0-1
	GTF2IRD2B	NM_001368302.1		c.932C>T	p.Pro311Leu	missense	Exon 5 of 16	NP_001355231.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2IRD2B	ENST00000472837.7	TSL:1 MANE Select	c.446C>T	p.Pro149Leu	missense	Exon 5 of 16	ENSP00000480524.1	Q6EKJ0-1
	GTF2IRD2B	ENST00000619142.4	TSL:1	c.446C>T	p.Pro149Leu	missense	Exon 5 of 16	ENSP00000480037.1	A0A087WW90
	GTF2IRD2B	ENST00000418185.6	TSL:1	n.446C>T		non_coding_transcript_exon	Exon 5 of 15	ENSP00000411454.3	Q6EKJ0-2

Frequencies

GnomAD3 genomes AF: 0.0000778 AC: 10 AN: 128516 Hom.: 1 Cov.: 19

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000863

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000971

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000118 AC: 24 AN: 202548 AF XY: 0.0000984

Gnomad AFR exome AF: 0.0000759

Gnomad AMR exome AF: 0.0000442

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00115

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000208

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000703 AC: 96 AN: 1365596 Hom.: 0 Cov.: 25 AF XY: 0.0000591 AC XY: 40 AN XY: 677168

African (AFR) AF: 0.0000348 AC: 1 AN: 28766

American (AMR) AF: 0.0000304 AC: 1 AN: 32916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23788

East Asian (EAS) AF: 0.00172 AC: 67 AN: 38970

South Asian (SAS) AF: 0.0000383 AC: 3 AN: 78326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3820

European-Non Finnish (NFE) AF: 0.0000181 AC: 19 AN: 1051436

Other (OTH) AF: 0.0000886 AC: 5 AN: 56464

GnomAD4 genome AF: 0.0000778 AC: 10 AN: 128594 Hom.: 1 Cov.: 19 AF XY: 0.0000652 AC XY: 4 AN XY: 61376

African (AFR) AF: 0.00 AC: 0 AN: 31828

American (AMR) AF: 0.00 AC: 0 AN: 12612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3240

East Asian (EAS) AF: 0.000865 AC: 4 AN: 4622

South Asian (SAS) AF: 0.00 AC: 0 AN: 3906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.0000971 AC: 6 AN: 61810

Other (OTH) AF: 0.00 AC: 0 AN: 1710

Alfa AF: 0.0000970 Hom.: 0

ExAC AF: 0.0000915 AC: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.12
Eigen_PC	Benign	-0.085
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.36	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		5.0
PrimateAI	Uncertain	0.57	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.94		Loss of disorder (P = 0.1205)
MVP		0.32
ClinPred		0.38	T
GERP RS		3.1
Varity_R		0.42
gMVP		0.47
Mutation Taster		=86/14	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: rs782783918; hg19: chr7-74539024;