7-100681753-G-C

Variant names:

• chr7-100681753-G-C
• rs201843233
• NM_001375765.1:c.3074C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001375765.1(GIGYF1):​c.3074C>G​(p.Ser1025Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000698 in 1,432,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: GIGYF1 NM_001375765.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.93

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32166612).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF1	NM_001375765.1	c.3074C>G	p.Ser1025Cys	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.3074C>G	p.Ser1025Cys	missense_variant	Exon 27 of 27		NM_001375765.1	ENSP00000503354.1
GIGYF1	ENST00000275732.5	c.3074C>G	p.Ser1025Cys	missense_variant	Exon 24 of 24	1		ENSP00000275732.4
GIGYF1	ENST00000646601.1	c.3074C>G	p.Ser1025Cys	missense_variant	Exon 28 of 28			ENSP00000494292.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000442 AC: 1 AN: 226364 Hom.: 0 AF XY: 0.00000824 AC XY: 1 AN XY: 121418

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000977

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432268 Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1 AN XY: 709250

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: 9.12e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	0.0077	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Benign	0.95
DEOGEN2	Benign	0.33	T;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.78	.;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Uncertain	0.30	D
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.7	D;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.0070	D;.
Sift4G	Uncertain	0.0060	D;.
Polyphen		0.66	P;P
Vest4		0.22
MutPred		0.23		Loss of disorder (P = 0.0043);Loss of disorder (P = 0.0043);
MVP		0.42
MPC		0.72
ClinPred		0.87	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.24
gMVP		0.67

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: rs201843233; hg19: chr7-100279376;