7-832531-T-G

Variant names:

• chr7-832531-T-G
• rs1562542721
• NM_001130965.3:c.7T>G

Variant summary

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

The NM_001367635.1(SUN1):​c.-451T>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000657 in 152,180 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SUN1 NM_001367635.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.56
• 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_001367635.1. 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.7T>G	p.Phe3Val	missense	Exon 1 of 19	NP_001124437.1	O94901-8
	SUN1	NM_001367635.1		c.-451T>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 21	NP_001354564.1
	SUN1	NM_001367705.1		c.7T>G	p.Phe3Val	missense	Exon 2 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.7T>G	p.Phe3Val	missense	Exon 1 of 19	ENSP00000384015.1	O94901-8
	SUN1	ENST00000457378.6	TSL:1	c.70T>G	p.Phe24Val	missense	Exon 3 of 7	ENSP00000395952.2	O94901-7
	SUN1	ENST00000425407.6	TSL:5	c.-144T>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	ENSP00000392309.2	O94901-5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.57	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	0.97	L
PhyloP100		5.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Vest4		0.76
MutPred		0.28		Gain of disorder (P = 0.1426)
MVP		0.34
MPC		0.30
ClinPred		0.99	D
GERP RS		4.9
PromoterAI		0.044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.48
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs1562542721; hg19: chr7-872168;