17-31434036-T-G

Variant names:

• chr17-31434036-T-G
• rs887379998
• NM_032932.6:c.250T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032932.6(RAB11FIP4):​c.250T>G​(p.Cys84Gly) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. C84R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAB11FIP4 NM_032932.6 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96
• Publications: 0 publications found

Genes affected

RAB11FIP4 (HGNC:30267): (RAB11 family interacting protein 4) The protein encoded by this gene interacts with RAB11 and is thought to be involved in bringing recycling endosome membranes to the cleavage furrow in late cytokinesis. Hypoxic conditions can lead to an upregulation of the encoded protein and enhance the metastatic potential of hepatocellular carcinoma. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032932.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB11FIP4	NM_032932.6	MANE Select	c.250T>G	p.Cys84Gly	missense splice_region	Exon 3 of 15	NP_116321.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB11FIP4	ENST00000621161.5	TSL:1 MANE Select	c.250T>G	p.Cys84Gly	missense splice_region	Exon 3 of 15	ENSP00000482620.1	Q86YS3-1
	RAB11FIP4	ENST00000964368.1		c.250T>G	p.Cys84Gly	missense splice_region	Exon 3 of 15	ENSP00000634427.1
	RAB11FIP4	ENST00000582009.5	TSL:3	c.118T>G	p.Cys40Gly	missense splice_region	Exon 3 of 5	ENSP00000463206.1	J3QKR9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	23
DANN	Benign	0.68
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.0
PrimateAI	Uncertain	0.50	T
Sift4G	Benign	0.84	T
Polyphen		1.0	D
Vest4		0.84
MutPred		0.51		Gain of disorder (P = 0.023)
MVP		0.37
ClinPred		0.67	D
GERP RS		4.8
Varity_R		0.21
gMVP		0.66

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

Other links and lift over

dbSNP: rs887379998; hg19: chr17-29761054;