rs576725260

Variant names:

• chr7-100681733-C-A
• rs576725260
• NM_001375765.1:c.3094G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-100681733-C-A
• chr7-100681733-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001375765.1(GIGYF1):​c.3094G>T​(p.Val1032Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1032M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GIGYF1 NM_001375765.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98

Genes affected

GIGYF1 (HGNC:9126): (GRB10 interacting GYF protein 1) This gene encodes a member of the gyf family of adaptor proteins. The encoded protein contains a gyf protein interaction domain. It binds growth factor receptor bound 10, another adaptor protein that binds activated insulin-like growth factor 1 and insulin receptors and regulates receptor signaling. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08695108).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF1	NM_001375765.1	c.3094G>T	p.Val1032Leu	missense_variant	Exon 27 of 27	ENST00000678049.1	NP_001362694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIGYF1	ENST00000678049.1	c.3094G>T	p.Val1032Leu	missense_variant	Exon 27 of 27		NM_001375765.1	ENSP00000503354.1
GIGYF1	ENST00000275732.5	c.3094G>T	p.Val1032Leu	missense_variant	Exon 24 of 24	1		ENSP00000275732.4
GIGYF1	ENST00000646601.1	c.3094G>T	p.Val1032Leu	missense_variant	Exon 28 of 28			ENSP00000494292.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1421076 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 702604

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.064	T;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.81	.;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.087	T;T
MetaSVM	Benign	-0.72	T
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.88	N;.
REVEL	Uncertain	0.45
Sift	Benign	0.84	T;.
Sift4G	Benign	0.41	T;.
Polyphen		0.0020	B;B
Vest4		0.32
MutPred		0.14		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP		0.87
MPC		0.35
ClinPred		0.28	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.090
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs576725260; hg19: chr7-100279356;