17-31391874-T-A

Variant names:

• chr17-31391874-T-A
• rs1419946427
• NM_032932.6:c.22T>A

Variant summary

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

The NM_032932.6(RAB11FIP4):​c.22T>A​(p.Ser8Thr) 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. 12/19 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. S8A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RAB11FIP4 NM_032932.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• 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]

ENSG00000306303 (HGNC:):

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=0.038128793).

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.22T>A	p.Ser8Thr	missense	Exon 1 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.22T>A	p.Ser8Thr	missense	Exon 1 of 15	ENSP00000482620.1	Q86YS3-1
	RAB11FIP4	ENST00000964368.1		c.22T>A	p.Ser8Thr	missense	Exon 1 of 15	ENSP00000634427.1
	ENSG00000306303	ENST00000816883.1		n.170+388A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1027724 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 488510

African (AFR) AF: 0.00 AC: 0 AN: 20538

American (AMR) AF: 0.00 AC: 0 AN: 6226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11358

East Asian (EAS) AF: 0.00 AC: 0 AN: 20536

South Asian (SAS) AF: 0.00 AC: 0 AN: 20506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2594

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 888920

Other (OTH) AF: 0.00 AC: 0 AN: 39114

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	20
DANN	Benign	0.42
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.19	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.069
PrimateAI	Pathogenic	0.91	D
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.089
MutPred		0.16		Loss of glycosylation at S8 (P = 0.0089)
MVP		0.068
ClinPred		0.028	T
GERP RS		1.7
PromoterAI		-0.072	Neutral
Varity_R		0.064
gMVP		0.21

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: rs1419946427; hg19: chr17-29718892;