chr15-48878241-T-C

Variant names:

• chr15-48878241-T-C
• rs760215753
• NM_014335.3:c.65T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014335.3(EID1):​c.65T>C​(p.Met22Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000096 in 1,458,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: EID1 NM_014335.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.99
• Publications: 0 publications found

Genes affected

EID1 (HGNC:1191): (EP300 interacting inhibitor of differentiation 1) Enables histone acetyltransferase binding activity and histone acetyltransferase regulator activity. Involved in cell differentiation and negative regulation of transcription, DNA-templated. Acts upstream of or within negative regulation of transcription by RNA polymerase II. Located in cytoplasmic ribonucleoprotein granule and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SHC4 (HGNC:16743): (SHC adaptor protein 4) Predicted to enable receptor tyrosine kinase binding activity. Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within several processes, including apoptotic process; positive regulation of cell population proliferation; and stem cell differentiation. Predicted to be located in postsynaptic membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.099462986).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014335.3. 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
	EID1	NM_014335.3	MANE Select	c.65T>C	p.Met22Thr	missense	Exon 1 of 1	NP_055150.1	Q9Y6B2-1
	SHC4	NM_203349.4	MANE Select	c.840+6007A>G		intron	N/A	NP_976224.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EID1	ENST00000530028.3	TSL:6 MANE Select	c.65T>C	p.Met22Thr	missense	Exon 1 of 1	ENSP00000431162.2	Q9Y6B2-1
	SHC4	ENST00000332408.9	TSL:1 MANE Select	c.840+6007A>G		intron	N/A	ENSP00000329668.4	Q6S5L8-1
	EID1	ENST00000560490.1	TSL:3	c.65T>C	p.Met22Thr	missense	Exon 1 of 2	ENSP00000453886.1	H0YN68

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000284 AC: 7 AN: 246268 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000204

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: 0.00

GnomAD4 exome AF: 0.00000960 AC: 14 AN: 1458072 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 725036

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.000180 AC: 8 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25774

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 85674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53204

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5748

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1109816

Other (OTH) AF: 0.0000166 AC: 1 AN: 60226

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000248 AC: 3

ClinVar

ClinVar submissions as Germline

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	Pathogenic	0.58
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.026
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.0
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.076
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.023	D
Polyphen		0.28	B
Vest4		0.31
MutPred		0.18		Gain of phosphorylation at M22 (P = 0.0336)
MVP		0.10
MPC		0.31
ClinPred		0.34	T
GERP RS		4.1
PromoterAI		0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.70
gMVP		0.091
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs760215753; hg19: chr15-49170438;