7-47996054-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001030019.2(SUN3):​c.670A>G​(p.Met224Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000701 in 1,425,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M224L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SUN3 NM_001030019.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.75

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23103413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN3	NM_001030019.2	c.670A>G	p.Met224Val	missense_variant	Exon 7 of 10	ENST00000297325.9	NP_001025190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUN3	ENST00000297325.9	c.670A>G	p.Met224Val	missense_variant	Exon 7 of 10	5	NM_001030019.2	ENSP00000297325.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1425574 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 709152

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000170

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.018	T;.;.;T;.;.
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.78	.;T;T;T;T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.23	T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.3	L;.;.;L;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.3	N;N;.;N;N;.
REVEL	Benign	0.12
Sift	Benign	0.098	T;T;.;T;T;.
Sift4G	Benign	0.57	T;T;T;T;T;T
Polyphen		0.42	B;.;.;B;P;.
Vest4		0.39
MutPred		0.52		Loss of catalytic residue at M224 (P = 0.1155);.;.;Loss of catalytic residue at M224 (P = 0.1155);.;.;
MVP		0.52
MPC		0.15
ClinPred		0.71	D
GERP RS		5.3
Varity_R		0.21
gMVP		0.44

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: rs755295610; hg19: chr7-48035651;