rs375757497

Variant names:

• chr9-35075742-G-A
• rs375757497
• NM_004629.2:c.1156C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-35075742-G-A
• chr9-35075742-G-C
• chr9-35075742-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004629.2(FANCG):​c.1156C>T​(p.Pro386Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 450,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. P386R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: FANCG NM_004629.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.799
• Publications: 2 publications found

Genes affected

FANCG (HGNC:3588): (FA complementation group G) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group G. [provided by RefSeq, Jul 2008]

FANCG Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group G

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03592795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCG	NM_004629.2	c.1156C>T	p.Pro386Ser	missense_variant	Exon 10 of 14	ENST00000378643.8	NP_004620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCG	ENST00000378643.8	c.1156C>T	p.Pro386Ser	missense_variant	Exon 10 of 14	1	NM_004629.2	ENSP00000367910.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00000859 AC: 2 AN: 232908 AF XY: 0.0000157

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000306

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000948

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000111 AC: 5 AN: 450126 Hom.: 0 Cov.: 0 AF XY: 0.00000820 AC XY: 2 AN XY: 244032

African (AFR) AF: 0.00 AC: 0 AN: 12276

American (AMR) AF: 0.0000279 AC: 1 AN: 35902

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13482

East Asian (EAS) AF: 0.00 AC: 0 AN: 17300

South Asian (SAS) AF: 0.00 AC: 0 AN: 67228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3102

European-Non Finnish (NFE) AF: 0.0000161 AC: 4 AN: 249146

Other (OTH) AF: 0.00 AC: 0 AN: 20358

GnomAD4 genome Cov.: 29

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	2.9
DANN	Benign	0.61
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.80
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.062
Sift	Benign	0.85	T
Sift4G	Benign	0.74	T
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.21		Gain of phosphorylation at P386 (P = 0.0065);
MVP		0.37
MPC		0.21
ClinPred		0.016	T
GERP RS		1.4
Varity_R		0.014
gMVP		0.12
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs375757497; hg19: chr9-35075739;