7-861385-A-G

Variant names:

• chr7-861385-A-G
• NM_001130965.3:c.1785A>G
• SUN1 p.Ala595Ala

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001130965.3(SUN1):​c.1785A>G​(p.Ala595Ala) 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. A595A) 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: -0.846
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.019).
• BP7: Synonymous conserved (PhyloP=-0.846 with no splicing effect.

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.1785A>G	p.Ala595Ala	synonymous	Exon 15 of 19	NP_001124437.1	O94901-8
	SUN1	NM_001367651.1		c.2199A>G	p.Ala733Ala	synonymous	Exon 18 of 22	NP_001354580.1
	SUN1	NM_001367705.1		c.2178A>G	p.Ala726Ala	synonymous	Exon 19 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.1785A>G	p.Ala595Ala	synonymous	Exon 15 of 19	ENSP00000384015.1	O94901-8
	SUN1	ENST00000429178.5	TSL:1	c.1560A>G	p.Ala520Ala	synonymous	Exon 13 of 17	ENSP00000409909.1	H0Y742
	SUN1	ENST00000475971.5	TSL:1	n.1894A>G		non_coding_transcript_exon	Exon 6 of 10

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.045
DANN	Benign	0.35
PhyloP100		-0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-901022;