chr5-179550595-C-T

Variant names:

• chr5-179550595-C-T
• rs773239258
• NM_025158.5:c.26C>T

Variant summary

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

The NM_025158.5(RUFY1):​c.26C>T​(p.Ala9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,344,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000041 (0 hom., cov: 35)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: RUFY1 NM_025158.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.784
• Publications: 1 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: 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=0.032512635).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025158.5. 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
	RUFY1	NM_025158.5	MANE Select	c.26C>T	p.Ala9Val	missense	Exon 1 of 18	NP_079434.3
	LOC128966623	NR_185480.1		n.783+25880C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUFY1	ENST00000319449.9	TSL:1 MANE Select	c.26C>T	p.Ala9Val	missense	Exon 1 of 18	ENSP00000325594.4	Q96T51-1
	RUFY1	ENST00000891455.1		c.26C>T	p.Ala9Val	missense	Exon 1 of 19	ENSP00000561514.1
	RUFY1	ENST00000954263.1		c.26C>T	p.Ala9Val	missense	Exon 1 of 18	ENSP00000624322.1

Frequencies

GnomAD3 genomes AF: 0.0000415 AC: 5 AN: 120550 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000871

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000151 AC: 1 AN: 66276 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000392

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000327 AC: 40 AN: 1223820 Hom.: 0 Cov.: 35 AF XY: 0.0000383 AC XY: 23 AN XY: 601228

African (AFR) AF: 0.00 AC: 0 AN: 24646

American (AMR) AF: 0.00 AC: 0 AN: 21256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19650

East Asian (EAS) AF: 0.00 AC: 0 AN: 26242

South Asian (SAS) AF: 0.00 AC: 0 AN: 58690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3644

European-Non Finnish (NFE) AF: 0.0000383 AC: 38 AN: 992280

Other (OTH) AF: 0.0000410 AC: 2 AN: 48832

GnomAD4 genome AF: 0.0000415 AC: 5 AN: 120550 Hom.: 0 Cov.: 35 AF XY: 0.0000339 AC XY: 2 AN XY: 58918

African (AFR) AF: 0.00 AC: 0 AN: 27686

American (AMR) AF: 0.00 AC: 0 AN: 12892

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2968

East Asian (EAS) AF: 0.00 AC: 0 AN: 4614

South Asian (SAS) AF: 0.00 AC: 0 AN: 3926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 250

European-Non Finnish (NFE) AF: 0.0000871 AC: 5 AN: 57436

Other (OTH) AF: 0.00 AC: 0 AN: 1698

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000108 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.1
DANN	Benign	0.82
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.14	N
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.78
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.023
Sift	Benign	0.24	T
Sift4G	Benign	0.64	T
Polyphen		0.0020	B
Vest4		0.21
MutPred		0.33		Gain of sheet (P = 0.0477)
MVP		0.29
MPC		0.22
ClinPred		0.062	T
GERP RS		0.12
PromoterAI		-0.081	Neutral
Varity_R		0.031
gMVP		0.18
Mutation Taster		=99/1	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: rs773239258; hg19: chr5-178977596; COSMIC: COSV100106641; COSMIC: COSV100106641;