chr20-56516948-C-T

Position:

• chr20-56516948-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016407.5(RTF2):​c.605C>T​(p.Pro202Leu) 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. 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)
• Consequence: RTF2 NM_016407.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18349254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTF2	NM_016407.5	c.605C>T	p.Pro202Leu	missense_variant	7/9	ENST00000357348.10
GCNT7	NR_160308.1	n.144-2643G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTF2	ENST00000357348.10	c.605C>T	p.Pro202Leu	missense_variant	7/9	1	NM_016407.5	P1
GCNT7	ENST00000243913.8	c.-929-2643G>A		intron_variant		2		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Aug 17, 2021

The c.605C>T (p.P202L) alteration is located in exon 7 (coding exon 7) of the RTFDC1 gene. This alteration results from a C to T substitution at nucleotide position 605, causing the proline (P) at amino acid position 202 to be replaced by a leucine (L). 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	0.084
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.013	.;.;T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.038
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.0	.;.;N
REVEL	Benign	0.045
Sift	Benign	0.26	.;.;T
Sift4G	Benign	0.28	T;T;T
Vest4		0.17
MutPred		0.35		Loss of glycosylation at P232 (P = 0.0202);.;Loss of glycosylation at P232 (P = 0.0202);
MVP		0.47
MPC		0.33
ClinPred		0.69	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.15

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: chr20-55092004;