17-31528726-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_032932.6(RAB11FIP4):c.1601A>G(p.Asn534Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,459,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: RAB11FIP4 NM_032932.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.379

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0205535).
• BS2: High AC in GnomAdExome at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB11FIP4	NM_032932.6	c.1601A>G	p.Asn534Ser	missense_variant	13/15	ENST00000621161.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB11FIP4	ENST00000621161.5	c.1601A>G	p.Asn534Ser	missense_variant	13/15	1	NM_032932.6	P1
RAB11FIP4	ENST00000394744.6	c.1295A>G	p.Asn432Ser	missense_variant	11/13	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000364 AC: 9 AN: 247582 Hom.: 0 AF XY: 0.0000298 AC XY: 4 AN XY: 134362

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000199 AC: 29 AN: 1459742 Hom.: 0 Cov.: 32 AF XY: 0.0000207 AC XY: 15 AN XY: 726144

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000153

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000453

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000330 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2021

The c.1601A>G (p.N534S) alteration is located in exon 13 (coding exon 13) of the RAB11FIP4 gene. This alteration results from a A to G substitution at nucleotide position 1601, causing the asparagine (N) at amino acid position 534 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	Benign	0.049
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	6.0
Dann	Benign	0.79
DEOGEN2	Benign	0.25	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.021	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;.
MutationTaster	Benign	0.98	D;D
PrimateAI	Benign	0.36	T
Sift4G	Benign	0.24	T;T
Polyphen		0.0020	B;B
Vest4		0.094
MutPred		0.15		Gain of phosphorylation at N534 (P = 0.0238);.;
MVP		0.10
ClinPred		0.017	T
GERP RS		-1.5
Varity_R		0.072
gMVP		0.28

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

LitVar

Other links and lift over

dbSNP: rs748838921; hg19: chr17-29855744;