NM_025158.5:c.212G>A

Variant names:

• chr5-179550781-G-A
• rs768128345
• NM_025158.5:c.212G>A

Variant summary

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

The NM_025158.5(RUFY1):​c.212G>A​(p.Arg71His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000324 in 1,233,234 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R71L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: RUFY1 NM_025158.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45
• Publications: 0 publications found

Genes affected

RUFY1 (HGNC:19760): (RUN and FYVE domain containing 1) This gene encodes a protein that contains a RUN domain and a FYVE-type zinc finger domain. The encoded protein binds to phosphatidylinositol-3-phosphate (PI3P) and plays a role in early endosomal trafficking, tethering and fusion through interactions with small GTPases including Rab4, Rab5 and Rab14. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

LOC128966623 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
RUFY1	NM_025158.5	c.212G>A	p.Arg71His	missense_variant	Exon 1 of 18	ENST00000319449.9	NP_079434.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUFY1	ENST00000319449.9	c.212G>A	p.Arg71His	missense_variant	Exon 1 of 18	1	NM_025158.5	ENSP00000325594.4
RUFY1	ENST00000393448.6	n.-56G>A		upstream_gene_variant		1		ENSP00000377094.2
RUFY1	ENST00000502984.5	c.-59G>A		upstream_gene_variant		3		ENSP00000425533.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000324 AC: 4 AN: 1233234 Hom.: 0 Cov.: 35 AF XY: 0.00000330 AC XY: 2 AN XY: 605820

African (AFR) AF: 0.00 AC: 0 AN: 25356

American (AMR) AF: 0.00 AC: 0 AN: 22004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20548

East Asian (EAS) AF: 0.00 AC: 0 AN: 26350

South Asian (SAS) AF: 0.00 AC: 0 AN: 59858

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3986

European-Non Finnish (NFE) AF: 0.00000401 AC: 4 AN: 996368

Other (OTH) AF: 0.00 AC: 0 AN: 49430

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.061	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.70	D
M_CAP	Pathogenic	0.81	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.4
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.079
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.050	T
Polyphen		0.97	D
Vest4		0.41
MutPred		0.42		Loss of MoRF binding (P = 0.0132);
MVP		0.76
MPC		0.47
ClinPred		0.89	D
GERP RS		3.0
PromoterAI		-0.015	Neutral
Varity_R		0.12
gMVP		0.46
Mutation Taster		=85/15	polymorphism

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: rs768128345; hg19: chr5-178977782;