NM_001375765.1:c.3094G>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/21 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
• Publications: 1 publications found

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]

GIGYF1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375765.1. 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
	GIGYF1	NM_001375765.1	MANE Select	c.3094G>T	p.Val1032Leu	missense	Exon 27 of 27	NP_001362694.1	O75420
	GIGYF1	NM_001375766.1		c.3094G>T	p.Val1032Leu	missense	Exon 28 of 28	NP_001362695.1	O75420
	GIGYF1	NM_001375759.1		c.3186G>T	p.Ala1062Ala	synonymous	Exon 26 of 26	NP_001362688.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIGYF1	ENST00000678049.1	MANE Select	c.3094G>T	p.Val1032Leu	missense	Exon 27 of 27	ENSP00000503354.1	O75420
	GIGYF1	ENST00000275732.5	TSL:1	c.3094G>T	p.Val1032Leu	missense	Exon 24 of 24	ENSP00000275732.4	O75420
	GIGYF1	ENST00000893817.1		c.3127G>T	p.Val1043Leu	missense	Exon 27 of 27	ENSP00000563876.1

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

African (AFR) AF: 0.00 AC: 0 AN: 32608

American (AMR) AF: 0.00 AC: 0 AN: 39932

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39400

South Asian (SAS) AF: 0.00 AC: 0 AN: 79406

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5560

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091222

Other (OTH) AF: 0.00 AC: 0 AN: 58640

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.72	T
PhyloP100		2.0
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
Vest4		0.32
MutPred		0.14		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
Mutation Taster		=76/22	polymorphism

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

Other links and lift over

dbSNP: rs576725260; hg19: chr7-100279356;