NM_001130965.3:c.16C>T

Variant names:

• chr7-832540-C-T
• rs777969470
• NM_001130965.3:c.16C>T

Variant summary

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

The NM_001130965.3(SUN1):​c.16C>T​(p.Leu6Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,092 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L6I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SUN1 NM_001130965.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.48
• 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.16C>T	p.Leu6Phe	missense	Exon 1 of 19	NP_001124437.1	O94901-8
	SUN1	NM_001367705.1		c.16C>T	p.Leu6Phe	missense	Exon 2 of 23	NP_001354634.1	O94901-9
	SUN1	NM_001367678.1		c.16C>T	p.Leu6Phe	missense	Exon 2 of 23	NP_001354607.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN1	ENST00000401592.6	TSL:1 MANE Select	c.16C>T	p.Leu6Phe	missense	Exon 1 of 19	ENSP00000384015.1	O94901-8
	SUN1	ENST00000457378.6	TSL:1	c.79C>T	p.Leu27Phe	missense	Exon 3 of 7	ENSP00000395952.2	O94901-7
	SUN1	ENST00000963118.1		c.16C>T	p.Leu6Phe	missense	Exon 2 of 24	ENSP00000633177.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461092 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726726

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111616

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Benign	0.55	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	0.97	L
PhyloP100		5.5
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Vest4		0.74
MutPred		0.36		Loss of stability (P = 0.1096)
MVP		0.34
MPC		0.48
ClinPred		0.98	D
GERP RS		4.9
PromoterAI		0.013	Neutral
gMVP		0.44
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs777969470; hg19: chr7-872177;