chr1-8013367-A-G

Variant names:

• chr1-8013367-A-G
• NM_018948.4:c.1232T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018948.4(ERRFI1):​c.1232T>C​(p.Phe411Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ERRFI1 NM_018948.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96

Genes affected

ERRFI1 (HGNC:18185): (ERBB receptor feedback inhibitor 1) ERRFI1 is a cytoplasmic protein whose expression is upregulated with cell growth (Wick et al., 1995 [PubMed 7641805]). It shares significant homology with the protein product of rat gene-33, which is induced during cell stress and mediates cell signaling (Makkinje et al., 2000 [PubMed 10749885]; Fiorentino et al., 2000 [PubMed 11003669]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERRFI1	NM_018948.4	c.1232T>C	p.Phe411Ser	missense_variant	Exon 4 of 4	ENST00000377482.10	NP_061821.1
ERRFI1	XM_047422698.1	c.1232T>C	p.Phe411Ser	missense_variant	Exon 3 of 3		XP_047278654.1
ERRFI1	XM_005263477.4	c.1079T>C	p.Phe360Ser	missense_variant	Exon 3 of 3		XP_005263534.1
ERRFI1	XM_047422701.1	c.1007T>C	p.Phe336Ser	missense_variant	Exon 2 of 2		XP_047278657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERRFI1	ENST00000377482.10	c.1232T>C	p.Phe411Ser	missense_variant	Exon 4 of 4	1	NM_018948.4	ENSP00000366702.5
ERRFI1	ENST00000474874.5	c.125+2128T>C		intron_variant	Intron 2 of 2	3		ENSP00000466958.1
ERRFI1	ENST00000467067.1	c.*1903T>C		downstream_gene_variant		2		ENSP00000465100.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1232T>C (p.F411S) alteration is located in exon 4 (coding exon 3) of the ERRFI1 gene. This alteration results from a T to C substitution at nucleotide position 1232, causing the phenylalanine (F) at amino acid position 411 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.74	D
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.29
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.99	D
Vest4		0.55
MutPred		0.48		Gain of disorder (P = 0.0083);
MVP		0.80
MPC		0.84
ClinPred		0.97	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.51
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-8073427;