7-843459-G-C

Variant names:

• chr7-843459-G-C
• rs374832216
• NM_001130965.3:c.597G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001130965.3(SUN1):​c.597G>C​(p.Thr199Thr) variant causes a synonymous 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. T199T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SUN1 NM_001130965.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.33
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.002).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN1	NM_001130965.3	MANE Select	c.597G>C	p.Thr199Thr	synonymous	Exon 5 of 19	NP_001124437.1
	SUN1	NM_001367635.1		c.140G>C	p.Arg47Pro	missense	Exon 6 of 21	NP_001354564.1
	SUN1	NM_001367651.1		c.816G>C	p.Thr272Thr	synonymous	Exon 6 of 22	NP_001354580.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN1	ENST00000401592.6	TSL:1 MANE Select	c.597G>C	p.Thr199Thr	synonymous	Exon 5 of 19	ENSP00000384015.1
	SUN1	ENST00000429178.5	TSL:1	c.90G>C	p.Thr30Thr	synonymous	Exon 1 of 17	ENSP00000409909.1
	SUN1	ENST00000457378.6	TSL:1	c.660G>C	p.Thr220Thr	synonymous	Exon 7 of 7	ENSP00000395952.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

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
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.010
DANN	Benign	0.58
PhyloP100		-4.3
PromoterAI		-0.0060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs374832216; hg19: chr7-883096;