2-241073344-A-G

Position:

• chr2-241073344-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001080437.3(SNED1):​c.3896A>G​(p.His1299Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,573,046 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.016 (67 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (68 hom.)
• Consequence: SNED1 NM_001080437.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.65

Genes affected

SNED1 (HGNC:24696): (sushi, nidogen and EGF like domains 1) Predicted to enable Notch binding activity. Predicted to be involved in cell-matrix adhesion. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

SNED1 (HGNC:):

MTERF4 (HGNC:28785): (mitochondrial transcription termination factor 4) Enables rRNA binding activity. Predicted to be involved in rRNA processing and regulation of transcription, DNA-templated. Predicted to act upstream of or within several processes, including mitochondrial transcription; protein targeting to mitochondrion; and ribosome assembly. Located in cytosol and mitochondrion. Part of mitochondrial large ribosomal subunit. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020317733).
• BP6: Variant 2-241073344-A-G is Benign according to our data. Variant chr2-241073344-A-G is described in ClinVar as [Benign]. Clinvar id is 787248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNED1	NM_001080437.3	c.3896A>G	p.His1299Arg	missense_variant	27/32	ENST00000310397.13	NP_001073906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNED1	ENST00000310397.13	c.3896A>G	p.His1299Arg	missense_variant	27/32	5	NM_001080437.3	ENSP00000308893.8

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2453 AN: 152206 Hom.: 66 Cov.: 33

Gnomad AFR AF: 0.0551

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00831

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0124

GnomAD3 exomes AF: 0.00362 AC: 664 AN: 183218 Hom.: 17 AF XY: 0.00256 AC XY: 251 AN XY: 98110

Gnomad AFR exome AF: 0.0561

Gnomad AMR exome AF: 0.00345

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000125

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000153

Gnomad OTH exome AF: 0.00304

GnomAD4 exome AF: 0.00174 AC: 2475 AN: 1420722 Hom.: 68 Cov.: 30 AF XY: 0.00151 AC XY: 1063 AN XY: 702810

Gnomad4 AFR exome AF: 0.0600

Gnomad4 AMR exome AF: 0.00422

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000994

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000104

Gnomad4 OTH exome AF: 0.00404

GnomAD4 genome AF: 0.0161 AC: 2456 AN: 152324 Hom.: 67 Cov.: 33 AF XY: 0.0155 AC XY: 1154 AN XY: 74488

Gnomad4 AFR AF: 0.0550

Gnomad4 AMR AF: 0.00830

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00335 Hom.: 33

Bravo AF: 0.0188

ESP6500AA AF: 0.0462 AC: 191

ESP6500EA AF: 0.000119 AC: 1

ExAC AF: 0.00338 AC: 399

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 20, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.0040
DANN	Benign	0.69
DEOGEN2	Benign	0.019	.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.34	T;T
MetaRNN	Benign	0.0020	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.44	N;N
REVEL	Benign	0.13
Sift	Benign	1.0	T;T
Sift4G	Benign	0.81	T;T
Polyphen		0.0	B;B
Vest4		0.020
MVP		0.62
MPC		0.48
ClinPred		0.013	T
GERP RS		-7.3
Varity_R		0.039
gMVP		0.15

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

LitVar

Other links and lift over

dbSNP: rs6708120; hg19: chr2-242012759;