rs200959228

Variant names:

• chr7-100681740-G-A
• rs200959228
• NM_001375765.1:c.3087C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-100681740-G-A
• chr7-100681740-G-C
• chr7-100681740-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001375759.1(GIGYF1):​c.3179C>T​(p.Ser1060Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,578,634 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 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. S1060W) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (1 hom.)
• Consequence: GIGYF1 NM_001375759.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.643

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF1	NM_001375765.1	c.3087C>T	p.Ile1029Ile	synonymous_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.3087C>T	p.Ile1029Ile	synonymous_variant	Exon 27 of 27		NM_001375765.1	ENSP00000503354.1
GIGYF1	ENST00000275732.5	c.3087C>T	p.Ile1029Ile	synonymous_variant	Exon 24 of 24	1		ENSP00000275732.4
GIGYF1	ENST00000646601.1	c.3087C>T	p.Ile1029Ile	synonymous_variant	Exon 28 of 28			ENSP00000494292.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152162 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000275 AC: 61 AN: 221696 Hom.: 1 AF XY: 0.000286 AC XY: 34 AN XY: 118802

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00300

Gnomad SAS exome AF: 0.000122

Gnomad FIN exome AF: 0.0000505

Gnomad NFE exome AF: 0.0000199

Gnomad OTH exome AF: 0.000189

GnomAD4 exome AF: 0.000114 AC: 163 AN: 1426354 Hom.: 1 Cov.: 32 AF XY: 0.000116 AC XY: 82 AN XY: 705836

Gnomad4 AFR exome AF: 0.000122

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00304

Gnomad4 SAS exome AF: 0.0000996

Gnomad4 FIN exome AF: 0.0000194

Gnomad4 NFE exome AF: 0.0000183

Gnomad4 OTH exome AF: 0.000170

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152280 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74472

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000604 Hom.: 0

Bravo AF: 0.000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.7
DANN	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs200959228; hg19: chr7-100279363;