7-873321-C-T

Variant names:

• chr7-873321-C-T
• rs755364227
• NM_001130965.3:c.2348C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001130965.3(SUN1):​c.2348C>T​(p.Pro783Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. P783H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SUN1 NM_001130965.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.76
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130965.3. 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
	SUN1	NM_001130965.3	MANE Select	c.2348C>T	p.Pro783Leu	missense	Exon 19 of 19	NP_001124437.1	O94901-8
	SUN1	NM_001367651.1		c.2762C>T	p.Pro921Leu	missense	Exon 22 of 22	NP_001354580.1
	SUN1	NM_001367705.1		c.2741C>T	p.Pro914Leu	missense	Exon 23 of 23	NP_001354634.1	O94901-9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN1	ENST00000401592.6	TSL:1 MANE Select	c.2348C>T	p.Pro783Leu	missense	Exon 19 of 19	ENSP00000384015.1	O94901-8
	SUN1	ENST00000429178.5	TSL:1	c.2123C>T	p.Pro708Leu	missense	Exon 17 of 17	ENSP00000409909.1	H0Y742
	SUN1	ENST00000475971.5	TSL:1	n.2457C>T		non_coding_transcript_exon	Exon 10 of 10

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.90	T
PhyloP100		3.8
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-8.5	D
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.88	P
Vest4		0.48
MVP		0.15
MPC		1.7
ClinPred		1.0	D
GERP RS		4.6
gMVP		0.92
Mutation Taster		=23/77	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: rs755364227; hg19: chr7-912958;