7-48007188-C-T

Variant names:

• chr7-48007188-C-T
• rs1789548163
• NM_001030019.2:c.469G>A

Variant summary

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

The NM_001030019.2(SUN3):​c.469G>A​(p.Val157Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SUN3 NM_001030019.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -5.82

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=0.09552482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN3	NM_001030019.2	c.469G>A	p.Val157Met	missense_variant	Exon 5 of 10	ENST00000297325.9	NP_001025190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUN3	ENST00000297325.9	c.469G>A	p.Val157Met	missense_variant	Exon 5 of 10	5	NM_001030019.2	ENSP00000297325.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.469G>A (p.V157M) alteration is located in exon 5 (coding exon 5) of the SUN3 gene. This alteration results from a G to A substitution at nucleotide position 469, causing the valine (V) at amino acid position 157 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.0020
DANN	Benign	0.91
DEOGEN2	Benign	0.0098	T;.;T;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0046	N
LIST_S2	Benign	0.51	.;T;T;T;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.096	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N;.;N;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.70	N;.;N;N;.
REVEL	Benign	0.051
Sift	Benign	0.049	D;.;D;D;.
Sift4G	Benign	0.10	T;T;T;T;T
Polyphen		0.0020	B;.;B;B;.
Vest4		0.25
MutPred		0.20		Gain of disorder (P = 0.1098);.;Gain of disorder (P = 0.1098);.;.;
MVP		0.061
MPC		0.066
ClinPred		0.28	T
GERP RS		-10
Varity_R		0.031
gMVP		0.26

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: rs1789548163; hg19: chr7-48046785;