5-34911698-T-C

Position:

• chr5-34911698-T-C

Variant summary

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

The NM_002853.4(RAD1):​c.422A>G​(p.Glu141Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAD1 NM_002853.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.93

Genes affected

RAD1 (HGNC:9806): (RAD1 checkpoint DNA exonuclease) This gene encodes a component of a heterotrimeric cell cycle checkpoint complex, known as the 9-1-1 complex, that is activated to stop cell cycle progression in response to DNA damage or incomplete DNA replication. The 9-1-1 complex is recruited by RAD17 to affected sites where it may attract specialized DNA polymerases and other DNA repair effectors. Alternatively spliced transcript variants of this gene have been described. [provided by RefSeq, Jan 2009]

TTC23L (HGNC:):

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=0.20152771).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD1	NM_002853.4	c.422A>G	p.Glu141Gly	missense_variant	4/6	ENST00000382038.7	NP_002844.1
RAD1	NR_026591.2	n.471A>G		non_coding_transcript_exon_variant	3/5
TTC23L	NR_169875.1	n.974-6666T>C		intron_variant, non_coding_transcript_variant
TTC23L	NR_169876.1	n.1048-6666T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD1	ENST00000382038.7	c.422A>G	p.Glu141Gly	missense_variant	4/6	1	NM_002853.4	ENSP00000371469	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jul 09, 2021

The c.422A>G (p.E141G) alteration is located in exon 4 (coding exon 3) of the RAD1 gene. This alteration results from a A to G substitution at nucleotide position 422, causing the glutamic acid (E) at amino acid position 141 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	0.27
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.053
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.80	.;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Benign	0.14
Sift	Benign	0.10	T;T
Sift4G	Benign	0.10	T;T
Polyphen		0.010	B;B
Vest4		0.23
MutPred		0.66		Loss of stability (P = 0.0139);Loss of stability (P = 0.0139);
MVP		0.34
MPC		0.099
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.40
gMVP		0.67

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: chr5-34911803;