chr20-56513390-A-G

Position:

• chr20-56513390-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016407.5(RTF2):​c.553A>G​(p.Arg185Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RTF2 NM_016407.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.53

Genes affected

RTF2 (HGNC:15890): (replication termination factor 2) Enables DNA binding activity. Involved in cellular response to hydroxyurea and regulation of DNA stability. Located in replication fork. [provided by Alliance of Genome Resources, Apr 2022]

GCNT7 (HGNC:16099): (glucosaminyl (N-acetyl) transferase family member 7) Predicted to enable acetylglucosaminyltransferase activity. Predicted to be involved in protein glycosylation. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTF2	NM_016407.5	c.553A>G	p.Arg185Gly	missense_variant	6/9	ENST00000357348.10
GCNT7	NR_160308.1	n.406+406T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTF2	ENST00000357348.10	c.553A>G	p.Arg185Gly	missense_variant	6/9	1	NM_016407.5	P1
GCNT7	ENST00000243913.8	c.-667+406T>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

May 13, 2024

The c.553A>G (p.R185G) alteration is located in exon 6 (coding exon 6) of the RTFDC1 gene. This alteration results from a A to G substitution at nucleotide position 553, causing the arginine (R) at amino acid position 185 to be replaced by a glycine (G). 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	0.30
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	.;.;T;T
Eigen	Benign	0.078
Eigen_PC	Benign	-0.055
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.53	D;D;D;D
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-4.3	.;.;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.0090	.;.;D;D
Sift4G	Uncertain	0.0080	D;D;D;D
Polyphen		0.94	.;.;P;.
Vest4		0.50
MutPred		0.64		Loss of MoRF binding (P = 0.0256);.;.;Loss of MoRF binding (P = 0.0256);
MVP		0.63
MPC		0.95
ClinPred		0.98	D
GERP RS		3.0
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-55088446; COSMIC: COSV99196455; COSMIC: COSV99196455;