chr2-241073314-G-A

Variant names:

• chr2-241073314-G-A
• rs6721345
• NM_001080437.3:c.3866G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080437.3(SNED1):​c.3866G>A​(p.Arg1289Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00588 in 1,573,840 control chromosomes in the GnomAD database, including 465 homozygotes. 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 (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1289W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.030 (232 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (233 hom.)
• Consequence: SNED1 NM_001080437.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414
• Publications: 12 publications found

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]

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015307963).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080437.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNED1	NM_001080437.3	MANE Select	c.3866G>A	p.Arg1289Gln	missense	Exon 27 of 32	NP_001073906.1
	MTERF4	NR_138463.2		n.5493C>T		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNED1	ENST00000310397.13	TSL:5 MANE Select	c.3866G>A	p.Arg1289Gln	missense	Exon 27 of 32	ENSP00000308893.8
	SNED1	ENST00000491761.1	TSL:1	n.1834G>A		non_coding_transcript_exon	Exon 2 of 2
	SNED1	ENST00000957411.1		c.3845G>A	p.Arg1282Gln	missense	Exon 27 of 32	ENSP00000627470.1

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4612 AN: 152226 Hom.: 231 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0229

GnomAD2 exomes AF: 0.00700 AC: 1298 AN: 185500 AF XY: 0.00540

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.00550

Gnomad ASJ exome AF: 0.00101

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000327

Gnomad OTH exome AF: 0.00545

GnomAD4 exome AF: 0.00325 AC: 4619 AN: 1421496 Hom.: 233 Cov.: 30 AF XY: 0.00278 AC XY: 1954 AN XY: 703258

African (AFR) AF: 0.114 AC: 3684 AN: 32400

American (AMR) AF: 0.00665 AC: 252 AN: 37918

Ashkenazi Jewish (ASJ) AF: 0.000670 AC: 17 AN: 25392

East Asian (EAS) AF: 0.00 AC: 0 AN: 37252

South Asian (SAS) AF: 0.000186 AC: 15 AN: 80518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50358

Middle Eastern (MID) AF: 0.00577 AC: 33 AN: 5724

European-Non Finnish (NFE) AF: 0.000159 AC: 174 AN: 1092962

Other (OTH) AF: 0.00753 AC: 444 AN: 58972

GnomAD4 genome AF: 0.0304 AC: 4629 AN: 152344 Hom.: 232 Cov.: 32 AF XY: 0.0293 AC XY: 2179 AN XY: 74490

African (AFR) AF: 0.105 AC: 4360 AN: 41578

American (AMR) AF: 0.0123 AC: 189 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68036

Other (OTH) AF: 0.0227 AC: 48 AN: 2116

Alfa AF: 0.00907 Hom.: 182

Bravo AF: 0.0349

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0954 AC: 389

ESP6500EA AF: 0.000120 AC: 1

ExAC AF: 0.00699 AC: 826

Asia WGS AF: 0.00520 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.87
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0074	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N
PhyloP100		0.41
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	0.47	T
Polyphen		0.0060	B
Vest4		0.030
MVP		0.26
MPC		0.45
ClinPred		0.0035	T
GERP RS		-1.4
Varity_R		0.025
gMVP		0.15
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs6721345; hg19: chr2-242012729;