rs148505917

Variant names:

• chrX-24054996-C-T
• rs148505917
• NM_001415.4:c.28C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-24054996-C-T
• chrX-24054996-C-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP6_Very_Strong BP7 BS2

The NM_001415.4(EIF2S3):​c.28C>T​(p.Leu10Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000251 in 1,209,117 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 104 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., 5 hem., cov: 23)
  • Exomes 𝑓: 0.00026 (0 hom. 99 hem.)
• Consequence: EIF2S3 NM_001415.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.90
• Publications: 0 publications found

Genes affected

EIF2S3 (HGNC:3267): (eukaryotic translation initiation factor 2 subunit gamma) The protein encoded by this gene is the largest subunit of a heterotrimeric GTP-binding protein involved in the recruitment of methionyl-tRNA(i) to the 40 S ribosomal subunit. [provided by RefSeq, Jan 2010]

EIF2S3 Gene-Disease associations (from GenCC):

• MEHMO syndrome

  Inheritance: XL, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp
• diabetes mellitus

  Inheritance: XL Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP6: Variant X-24054996-C-T is Benign according to our data. Variant chrX-24054996-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 810535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.9 with no splicing effect.
• BS2: High AC in GnomAd4 at 23 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001415.4. 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
	EIF2S3	NM_001415.4	MANE Select	c.28C>T	p.Leu10Leu	synonymous	Exon 1 of 12	NP_001406.1	P41091

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2S3	ENST00000253039.9	TSL:1 MANE Select	c.28C>T	p.Leu10Leu	synonymous	Exon 1 of 12	ENSP00000253039.4	P41091
	EIF2S3	ENST00000864815.1		c.28C>T	p.Leu10Leu	synonymous	Exon 1 of 12	ENSP00000534874.1
	EIF2S3	ENST00000971837.1		c.28C>T	p.Leu10Leu	synonymous	Exon 1 of 12	ENSP00000641896.1

Frequencies

GnomAD3 genomes AF: 0.000206 AC: 23 AN: 111463 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000978

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000955

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: 0.000358

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000110 AC: 20 AN: 181040 AF XY: 0.000166

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000223

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000255 AC: 280 AN: 1097654 Hom.: 0 Cov.: 30 AF XY: 0.000273 AC XY: 99 AN XY: 363200

African (AFR) AF: 0.000114 AC: 3 AN: 26400

American (AMR) AF: 0.00 AC: 0 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.0000554 AC: 3 AN: 54138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40008

Middle Eastern (MID) AF: 0.00170 AC: 7 AN: 4128

European-Non Finnish (NFE) AF: 0.000289 AC: 243 AN: 842097

Other (OTH) AF: 0.000521 AC: 24 AN: 46089

GnomAD4 genome AF: 0.000206 AC: 23 AN: 111463 Hom.: 0 Cov.: 23 AF XY: 0.000149 AC XY: 5 AN XY: 33649

African (AFR) AF: 0.0000978 AC: 3 AN: 30662

American (AMR) AF: 0.0000955 AC: 1 AN: 10466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3552

South Asian (SAS) AF: 0.00 AC: 0 AN: 2672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6037

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.000358 AC: 19 AN: 53012

Other (OTH) AF: 0.00 AC: 0 AN: 1500

Alfa AF: 0.000521 Hom.: 6

Bravo AF: 0.000200

EpiCase AF: 0.000818

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	6.6
DANN	Benign	0.93
PhyloP100		2.9
PromoterAI		-0.052	Neutral
Mutation Taster		=100/0	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: rs148505917; hg19: chrX-24073113;