rs775248112

Variant names:

• chr15-41189972-G-A
• rs775248112
• NM_001286441.2:c.1021C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-41189972-G-A
• chr15-41189972-G-C
• chr15-41189972-G-T

Variant summary

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

The NM_001286441.2(EXD1):​c.1021C>T​(p.Arg341Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,613,946 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R341H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (1 hom.)
• Consequence: EXD1 NM_001286441.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.51
• Publications: 0 publications found

Genes affected

EXD1 (HGNC:28507): (exonuclease 3'-5' domain containing 1) Predicted to enable RNA binding activity and protein homodimerization activity. Predicted to be involved in gene silencing by RNA and piRNA metabolic process. Predicted to be located in P granule. Predicted to be part of PET complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286441.2. 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
	EXD1	NM_001286441.2	MANE Select	c.1021C>T	p.Arg341Cys	missense	Exon 11 of 12	NP_001273370.1	Q8NHP7-3
	EXD1	NM_001385036.1		c.952C>T	p.Arg318Cys	missense	Exon 10 of 11	NP_001371965.1
	EXD1	NM_152596.4		c.847C>T	p.Arg283Cys	missense	Exon 9 of 10	NP_689809.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXD1	ENST00000458580.7	TSL:2 MANE Select	c.1021C>T	p.Arg341Cys	missense	Exon 11 of 12	ENSP00000415056.2	Q8NHP7-3
	EXD1	ENST00000314992.9	TSL:1	c.847C>T	p.Arg283Cys	missense	Exon 9 of 10	ENSP00000321029.5	Q8NHP7-1
	EXD1	ENST00000558881.1	TSL:2	n.399C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152098 Hom.: 0 Cov.: 32

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: 0.000176

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000756 AC: 19 AN: 251468 AF XY: 0.0000662

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000140 AC: 205 AN: 1461848 Hom.: 1 Cov.: 30 AF XY: 0.000136 AC XY: 99 AN XY: 727230

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000162 AC: 180 AN: 1111982

Other (OTH) AF: 0.000182 AC: 11 AN: 60392

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152098 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74284

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68024

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000132 Hom.: 0

Bravo AF: 0.0000831

ExAC AF: 0.0000824 AC: 10

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

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	Uncertain	0.50
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.099
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.5
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.71
MVP		0.46
MPC		0.25
ClinPred		0.31	T
GERP RS		2.0
Varity_R		0.16
gMVP		0.49
Mutation Taster		=90/10	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: rs775248112; hg19: chr15-41482170;