7-47996054-T-A

Variant names:

• chr7-47996054-T-A
• rs755295610
• NM_001030019.2:c.670A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001030019.2(SUN3):​c.670A>T​(p.Met224Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000241 in 1,577,780 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: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: SUN3 NM_001030019.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.75
• Publications: 1 publications found

Genes affected

SUN3 (HGNC:22429): (Sad1 and UNC84 domain containing 3) Predicted to enable protein-membrane adaptor activity. Predicted to be involved in nuclear envelope organization. Predicted to be integral component of nuclear inner membrane. Predicted to be part of meiotic nuclear membrane microtubule tethering complex. Predicted to be active in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08803177).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001030019.2. 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
	SUN3	NM_001030019.2	MANE Select	c.670A>T	p.Met224Leu	missense	Exon 7 of 10	NP_001025190.1	Q8TAQ9-1
	SUN3	NM_152782.4		c.670A>T	p.Met224Leu	missense	Exon 8 of 11	NP_689995.3
	SUN3	NM_001284350.2		c.634A>T	p.Met212Leu	missense	Exon 8 of 11	NP_001271279.1	Q8TAQ9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN3	ENST00000297325.9	TSL:5 MANE Select	c.670A>T	p.Met224Leu	missense	Exon 7 of 10	ENSP00000297325.4	Q8TAQ9-1
	SUN3	ENST00000395572.6	TSL:1	c.670A>T	p.Met224Leu	missense	Exon 8 of 11	ENSP00000378939.2	Q8TAQ9-1
	SUN3	ENST00000438771.5	TSL:1	c.370A>T	p.Met124Leu	missense	Exon 4 of 8	ENSP00000409077.1	Q8TAQ9-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000129 AC: 29 AN: 224930 AF XY: 0.0000900

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000969

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: 0.000552

GnomAD4 exome AF: 0.0000260 AC: 37 AN: 1425574 Hom.: 0 Cov.: 28 AF XY: 0.0000183 AC XY: 13 AN XY: 709152

African (AFR) AF: 0.00 AC: 0 AN: 31236

American (AMR) AF: 0.000907 AC: 33 AN: 36380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25186

East Asian (EAS) AF: 0.00 AC: 0 AN: 38500

South Asian (SAS) AF: 0.00 AC: 0 AN: 78996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097664

Other (OTH) AF: 0.0000680 AC: 4 AN: 58862

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74368

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000945

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

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	Benign	0.20
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Benign	0.90
DEOGEN2	Benign	0.014	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.8
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.13
Sift	Benign	0.17	T
Sift4G	Benign	0.52	T
Polyphen		0.14	B
Vest4		0.39
MutPred		0.49		Gain of relative solvent accessibility (P = 0.2629)
MVP		0.39
MPC		0.14
ClinPred		0.070	T
GERP RS		5.3
Varity_R		0.22
gMVP		0.38
Mutation Taster		=84/16	polymorphism

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: rs755295610; hg19: chr7-48035651;