rs770380501

Variant names:

• chr15-41190047-G-A
• rs770380501
• NM_001286441.2:c.946C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-41190047-G-A
• chr15-41190047-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001286441.2(EXD1):​c.946C>T​(p.Pro316Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: EXD1 NM_001286441.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.59
• 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 2 ACMG points.

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

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.946C>T	p.Pro316Ser	missense	Exon 11 of 12	NP_001273370.1	Q8NHP7-3
	EXD1	NM_001385036.1		c.877C>T	p.Pro293Ser	missense	Exon 10 of 11	NP_001371965.1
	EXD1	NM_152596.4		c.772C>T	p.Pro258Ser	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.946C>T	p.Pro316Ser	missense	Exon 11 of 12	ENSP00000415056.2	Q8NHP7-3
	EXD1	ENST00000314992.9	TSL:1	c.772C>T	p.Pro258Ser	missense	Exon 9 of 10	ENSP00000321029.5	Q8NHP7-1
	EXD1	ENST00000558881.1	TSL:2	n.324C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251490 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

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

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 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	Uncertain	0.44
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0068	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.6
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.25
Sift	Benign	0.061	T
Sift4G	Benign	0.14	T
Polyphen		0.89	P
Vest4		0.50
MutPred		0.55		Gain of helix (P = 0.0164)
MVP		0.50
MPC		0.13
ClinPred		0.67	D
GERP RS		6.2
Varity_R		0.22
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs770380501; hg19: chr15-41482245;