7-872560-C-G

Variant names:

• chr7-872560-C-G
• rs143543329
• NM_001130965.3:c.2239C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001130965.3(SUN1):​c.2239C>G​(p.Leu747Val) variant causes a missense, splice region 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. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L747L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SUN1 NM_001130965.3 missense, splice_region
• Scores: Splicing: ADA: 0.008321
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17738461).

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.2239C>G	p.Leu747Val	missense splice_region	Exon 18 of 19	NP_001124437.1	O94901-8
	SUN1	NM_001367651.1		c.2653C>G	p.Leu885Val	missense splice_region	Exon 21 of 22	NP_001354580.1
	SUN1	NM_001367705.1		c.2632C>G	p.Leu878Val	missense splice_region	Exon 22 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.2239C>G	p.Leu747Val	missense splice_region	Exon 18 of 19	ENSP00000384015.1	O94901-8
	SUN1	ENST00000429178.5	TSL:1	c.2014C>G	p.Leu672Val	missense splice_region	Exon 16 of 17	ENSP00000409909.1	H0Y742
	SUN1	ENST00000475971.5	TSL:1	n.2348C>G		splice_region non_coding_transcript_exon	Exon 9 of 10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1426062 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 705838

African (AFR) AF: 0.00 AC: 0 AN: 32858

American (AMR) AF: 0.00 AC: 0 AN: 39056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25426

East Asian (EAS) AF: 0.00 AC: 0 AN: 38216

South Asian (SAS) AF: 0.00 AC: 0 AN: 81134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1093376

Other (OTH) AF: 0.00 AC: 0 AN: 59064

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.5
DANN	Benign	0.72
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.053
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.9
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.10
Sift	Benign	0.36	T
Sift4G	Benign	0.71	T
Polyphen		0.080	B
Vest4		0.14
MVP		0.35
MPC		1.2
ClinPred		0.14	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.60
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0083
dbscSNV1_RF	Benign	0.19
SpliceAI score (max)		0.010		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: rs143543329; hg19: chr7-912197;