chr22-29214940-A-T

Position:

• chr22-29214940-A-T

Variant summary

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

The NM_133455.4(EMID1):​c.116A>T​(p.Tyr39Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000504 in 1,387,852 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: 0.0000050 (0 hom.)
• Consequence: EMID1 NM_133455.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

Genes affected

EMID1 (HGNC:18036): (EMI domain containing 1) Predicted to be located in several cellular components, including Golgi apparatus; endoplasmic reticulum; and extracellular matrix. Predicted to be part of collagen trimer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMID1	NM_133455.4	c.116A>T	p.Tyr39Phe	missense_variant	2/15	ENST00000334018.11	NP_597712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMID1	ENST00000334018.11	c.116A>T	p.Tyr39Phe	missense_variant	2/15	1	NM_133455.4	ENSP00000335481	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000504 AC: 7 AN: 1387852 Hom.: 0 Cov.: 31 AF XY: 0.00000731 AC XY: 5 AN XY: 683562

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000654

Gnomad4 OTH exome AF: 0.00

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

Apr 29, 2024

The c.116A>T (p.Y39F) alteration is located in exon 2 (coding exon 2) of the EMID1 gene. This alteration results from a A to T substitution at nucleotide position 116, causing the tyrosine (Y) at amino acid position 39 to be replaced by a phenylalanine (F). 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
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	0.97
DEOGEN2	Benign	0.17	.;T;T;T;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.85	T;D;D;D;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.61	D;D;D;D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.6	L;.;.;.;.
MutationTaster	Benign	0.84	N;N;N
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-2.1	N;D;N;N;D
REVEL	Benign	0.26
Sift	Benign	0.030	D;D;T;T;D
Sift4G	Benign	0.15	T;D;T;T;D
Polyphen		1.0	D;.;D;D;.
Vest4		0.53
MutPred		0.67		Loss of MoRF binding (P = 0.1006);Loss of MoRF binding (P = 0.1006);Loss of MoRF binding (P = 0.1006);Loss of MoRF binding (P = 0.1006);Loss of MoRF binding (P = 0.1006);
MVP		0.45
MPC		0.34
ClinPred		0.88	D
GERP RS		4.2
gMVP		0.29

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: chr22-29610929;