NM_001003795.3:c.311C>T

Variant names:

• chr7-75120963-C-T
• rs782309974
• NM_001003795.3:c.311C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001003795.3(GTF2IRD2B):​c.311C>T​(p.Thr104Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 152,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000090 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GTF2IRD2B NM_001003795.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.121
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03979197).

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.311C>T	p.Thr104Met	missense	Exon 4 of 16	NP_001003795.1	Q6EKJ0-1
	GTF2IRD2B	NM_001368302.1		c.797C>T	p.Thr266Met	missense	Exon 4 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.311C>T	p.Thr104Met	missense	Exon 4 of 16	ENSP00000480524.1	Q6EKJ0-1
	GTF2IRD2B	ENST00000619142.4	TSL:1	c.311C>T	p.Thr104Met	missense	Exon 4 of 16	ENSP00000480037.1	A0A087WW90
	GTF2IRD2B	ENST00000418185.6	TSL:1	n.311C>T		non_coding_transcript_exon	Exon 4 of 15	ENSP00000411454.3	Q6EKJ0-2

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152222 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000866 AC: 17 AN: 196298 AF XY: 0.0000832

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000469

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000903 AC: 132 AN: 1461574 Hom.: 0 Cov.: 30 AF XY: 0.0000894 AC XY: 65 AN XY: 727106

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000299 AC: 1 AN: 33468

American (AMR) AF: 0.000112 AC: 5 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86244

European-Finnish (FIN) AF: 0.000187 AC: 10 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000899 AC: 100 AN: 1111772

Other (OTH) AF: 0.000149 AC: 9 AN: 60378

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152222 Hom.: 0 Cov.: 28 AF XY: 0.0000538 AC XY: 4 AN XY: 74354

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000482 AC: 2 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5208

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68040

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000834 AC: 10

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	Benign	0.082
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.0081	N
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M
PhyloP100		0.12
PrimateAI	Benign	0.40	T
Sift4G	Benign	0.11	T
Polyphen		0.39	B
Vest4		0.23
MVP		0.030
ClinPred		0.025	T
GERP RS		2.0
Varity_R		0.030
gMVP		0.075
Mutation Taster		=98/2	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: rs782309974; hg19: chr7-74536764;