chr9-95150018-G-T

Variant names:

• chr9-95150018-G-T
• rs1457631500
• NM_000136.3:c.591C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_000136.3(FANCC):​c.591C>A​(p.Asp197Glu) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D197V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FANCC NM_000136.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 1.03
• Publications: 0 publications found

Genes affected

FANCC (HGNC:3584): (FA complementation group C) 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 C. [provided by RefSeq, Jul 2008]

AOPEP (HGNC:1361): (aminopeptidase O (putative)) This gene encodes a member of the M1 zinc aminopeptidase family. The encoded protein is a zinc-dependent metallopeptidase that catalyzes the removal of an amino acid from the amino terminus of a protein or peptide. This protein may play a role in the generation of angiotensin IV. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]

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=0.11137709).
• BP6: Variant 9-95150018-G-T is Benign according to our data. Variant chr9-95150018-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2446385.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000136.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCC	NM_000136.3	MANE Select	c.591C>A	p.Asp197Glu	missense	Exon 7 of 15	NP_000127.2
	FANCC	NM_001243743.2		c.591C>A	p.Asp197Glu	missense	Exon 7 of 15	NP_001230672.1
	FANCC	NM_001243744.2		c.591C>A	p.Asp197Glu	missense	Exon 7 of 14	NP_001230673.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCC	ENST00000289081.8	TSL:1 MANE Select	c.591C>A	p.Asp197Glu	missense	Exon 7 of 15	ENSP00000289081.3
	FANCC	ENST00000375305.6	TSL:1	c.591C>A	p.Asp197Glu	missense	Exon 7 of 15	ENSP00000364454.1
	FANCC	ENST00000490972.7	TSL:1	c.591C>A	p.Asp197Glu	missense	Exon 7 of 14	ENSP00000479931.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Fanconi anemia complementation group C Uncertain:1

King Fahd Medical Research Center, King Abdulaziz University

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

Hereditary cancer-predisposing syndrome Benign:1

Aug 19, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.6
DANN	Benign	0.78
DEOGEN2	Benign	0.049	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.9	N
PhyloP100		1.0
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.83	N
REVEL	Benign	0.093
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.083
MutPred		0.45		Gain of helix (P = 0.0696)
MVP		0.51
MPC		0.050
ClinPred		0.025	T
GERP RS		3.6
Varity_R		0.032
gMVP		0.079
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1457631500; hg19: chr9-97912300;