rs1334897032

Variant names:

• chr7-74822435-C-T
• rs1334897032
• NM_173537.5:c.563G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_173537.5(GTF2IRD2):​c.563G>A​(p.Ser188Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.000018 (0 hom., cov: 14)
  • Exomes 𝑓: 0.0000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GTF2IRD2 NM_173537.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.143
• Publications: 0 publications found

Genes affected

GTF2IRD2 (HGNC:30775): (GTF2I repeat domain containing 2) This gene is one of several closely related genes on chromosome 7 encoding proteins containing helix-loop-helix motifs. These proteins may function as regulators of transcription. The encoded protein is unique in that its C-terminus is derived from CHARLIE8 transposable element sequence. This gene is located in a region of chromosome 7 that is deleted in Williams-Beuren syndrome, and loss of this locus may contribute to the cognitive phenotypes observed in this disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ENSG00000289346 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04446733).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173537.5. 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
	GTF2IRD2	NM_173537.5	MANE Select	c.563G>A	p.Ser188Asn	missense	Exon 6 of 16	NP_775808.4
	GTF2IRD2	NM_001368300.2		c.1049G>A	p.Ser350Asn	missense	Exon 7 of 17	NP_001355229.1	A0A494C0I1
	GTF2IRD2	NM_001388079.1		c.563G>A	p.Ser188Asn	missense	Exon 6 of 16	NP_001375008.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2IRD2	ENST00000451013.7	TSL:1 MANE Select	c.563G>A	p.Ser188Asn	missense	Exon 6 of 16	ENSP00000406723.3	Q86UP8-1
	ENSG00000289346	ENST00000625377.3	TSL:5	c.563G>A	p.Ser188Asn	missense	Exon 13 of 23	ENSP00000486581.2
	GTF2IRD2	ENST00000651129.1		c.1049G>A	p.Ser350Asn	missense	Exon 7 of 17	ENSP00000498563.1	A0A494C0I1

Frequencies

GnomAD3 genomes AF: 0.0000185 AC: 2 AN: 108190 Hom.: 0 Cov.: 14

Gnomad AFR AF: 0.0000414

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000176

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000273 AC: 2 AN: 732948 Hom.: 0 Cov.: 10 AF XY: 0.00000258 AC XY: 1 AN XY: 387482

African (AFR) AF: 0.00 AC: 0 AN: 17530

American (AMR) AF: 0.00 AC: 0 AN: 36322

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20418

East Asian (EAS) AF: 0.00 AC: 0 AN: 33496

South Asian (SAS) AF: 0.00 AC: 0 AN: 68114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2652

European-Non Finnish (NFE) AF: 0.00000425 AC: 2 AN: 470730

Other (OTH) AF: 0.00 AC: 0 AN: 34978

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000185 AC: 2 AN: 108190 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 50218

African (AFR) AF: 0.0000414 AC: 1 AN: 24166

American (AMR) AF: 0.00 AC: 0 AN: 9116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2966

East Asian (EAS) AF: 0.00 AC: 0 AN: 3992

South Asian (SAS) AF: 0.00 AC: 0 AN: 2930

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5724

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.0000176 AC: 1 AN: 56934

Other (OTH) AF: 0.00 AC: 0 AN: 1336

Alfa AF: 0.00 Hom.: 0

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	0.067
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.2
DANN	Benign	0.90
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.14	N
PhyloP100		0.14
PrimateAI	Benign	0.39	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.099
MutPred		0.18		Loss of glycosylation at S188 (P = 0.0586)
MVP		0.014
ClinPred		0.33	T
GERP RS		-0.20
Varity_R		0.036
gMVP		0.038
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1334897032; hg19: chr7-74236963;