rs1006896977

chr7-852927-C-Gchr7-852927-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001130965.3(SUN1):c.1028C>G(p.Thr343Ser) 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. 12/17 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. T343I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SUN1 NM_001130965.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.581

Genes affected

SUN1 (HGNC:18587): (Sad1 and UNC84 domain containing 1) This gene is a member of the unc-84 homolog family and encodes a nuclear envelope protein with an Unc84 (SUN) domain. The protein is involved in nuclear anchorage and migration. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2019]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048696816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUN1	NM_001130965.3	c.1028C>G	p.Thr343Ser	missense_variant	9/19	ENST00000401592.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUN1	ENST00000401592.6	c.1028C>G	p.Thr343Ser	missense_variant	9/19	1	NM_001130965.3	P3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	2.9
Dann	Benign	0.23
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.31	N
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.049	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.60	N;N;N;N;N;N
REVEL	Benign	0.023
Sift	Benign	1.0	T;T;T;T;T;T
Sift4G	Benign	0.84	T;T;T;T;T;T
Polyphen		0.0040	B;.;.;.;B;.
Vest4		0.14
MVP		0.12
MPC		0.41
ClinPred		0.073	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1006896977; hg19: chr7-892564;