7-869411-G-C

Variant names:

• chr7-869411-G-C
• rs61744747
• NM_001130965.3:c.2043G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001130965.3(SUN1):​c.2043G>C​(p.Arg681Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R681R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SUN1 NM_001130965.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 9 publications found

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]

LOC124901568 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40438724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN1	NM_001130965.3	c.2043G>C	p.Arg681Ser	missense_variant	Exon 17 of 19	ENST00000401592.6	NP_001124437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUN1	ENST00000401592.6	c.2043G>C	p.Arg681Ser	missense_variant	Exon 17 of 19	1	NM_001130965.3	ENSP00000384015.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;.;T;.;.;T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.95	.;D;D;D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.40	T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
PhyloP100		-0.052
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.0	D;D;D;D;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.0040	D;D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D;D
Polyphen		0.97	D;.;.;.;D;.
Vest4		0.85
MVP		0.40
MPC		1.8
ClinPred		0.99	D
GERP RS		0.95
gMVP		0.93
Mutation Taster		=45/55	disease causing

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: rs61744747; hg19: chr7-909048;