rs1441937959

Variant names:

• chr15-82240555-T-A
• NM_024580.6:c.379A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-82240555-T-A
• chr15-82240555-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_024580.6(EFL1):​c.379A>T​(p.Thr127Ser) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: EFL1 NM_024580.6 missense, splice_region
• Scores: Splicing: ADA: 0.1287
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.45

Genes affected

EFL1 (HGNC:25789): (elongation factor like GTPase 1) Enables GTPase activity and ribosome binding activity. Involved in GTP metabolic process and mature ribosome assembly. Predicted to be part of ribonucleoprotein complex. Implicated in Shwachman-Diamond syndrome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFL1	NM_024580.6	c.379A>T	p.Thr127Ser	missense_variant, splice_region_variant	Exon 6 of 20	ENST00000268206.12	NP_078856.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFL1	ENST00000268206.12	c.379A>T	p.Thr127Ser	missense_variant, splice_region_variant	Exon 6 of 20	1	NM_024580.6	ENSP00000268206.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456990 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724540

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.77	T;T
M_CAP	Pathogenic	0.38	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Uncertain	0.61	D
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Pathogenic	0.89
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.92
MutPred		0.87		Loss of catalytic residue at T127 (P = 0.0444);.;
MVP		0.88
MPC		0.75
ClinPred		1.0	D
GERP RS		4.0
Varity_R		0.85
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.13
dbscSNV1_RF	Benign	0.44
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: -6

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: chr15-82532896;