chr3-47504433-T-C

Variant names:

• chr3-47504433-T-C
• rs150166753
• NM_001031703.3:c.220A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001031703.3(ELP6):​c.220A>G​(p.Met74Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000914 in 1,608,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000094 (0 hom.)
• Consequence: ELP6 NM_001031703.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.382
• Publications: 0 publications found

Genes affected

ELP6 (HGNC:25976): (elongator acetyltransferase complex subunit 6) Predicted to be involved in positive regulation of cell migration. Located in cytosol and nucleus. Part of elongator holoenzyme complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03182909).
• BP6: Variant 3-47504433-T-C is Benign according to our data. Variant chr3-47504433-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2570090.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP6	NM_001031703.3	c.220A>G	p.Met74Val	missense_variant	Exon 4 of 7	ENST00000296149.9	NP_001026873.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP6	ENST00000296149.9	c.220A>G	p.Met74Val	missense_variant	Exon 4 of 7	1	NM_001031703.3	ENSP00000296149.4

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000147 AC: 36 AN: 244210 AF XY: 0.000128

Gnomad AFR exome AF: 0.000131

Gnomad AMR exome AF: 0.000453

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000569

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000117

Gnomad OTH exome AF: 0.000681

GnomAD4 exome AF: 0.0000941 AC: 137 AN: 1455816 Hom.: 0 Cov.: 31 AF XY: 0.0000953 AC XY: 69 AN XY: 723916

African (AFR) AF: 0.0000300 AC: 1 AN: 33314

American (AMR) AF: 0.000385 AC: 17 AN: 44122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25992

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39396

South Asian (SAS) AF: 0.00 AC: 0 AN: 85416

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.0000992 AC: 110 AN: 1108602

Other (OTH) AF: 0.000133 AC: 8 AN: 60106

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152286 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74452

African (AFR) AF: 0.0000481 AC: 2 AN: 41554

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000570 Hom.: 0

Bravo AF: 0.0000831

ExAC AF: 0.000198 AC: 24

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Apr 18, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.0040
DANN	Benign	0.19
DEOGEN2	Benign	0.0077	T;T;T;T;T;T;T;T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.45	T;.;D;D;D;D;D;D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.020	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.41	N;.;.;.;.;.;.;.
PhyloP100		-0.38
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.16	N;N;N;N;N;N;N;N
REVEL	Benign	0.065
Sift	Benign	0.91	T;T;T;T;T;T;T;T
Sift4G	Benign	0.54	T;T;T;.;T;.;T;T
Polyphen		0.0	B;.;.;.;.;.;.;.
Vest4		0.14
MVP		0.35
MPC		0.37
ClinPred		0.0069	T
GERP RS		-11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.025
gMVP		0.21
Mutation Taster		=55/145	disease causing

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: rs150166753; hg19: chr3-47545923;