NM_001030019.2:c.232T>C

Variant names:

• chr7-48017318-A-G
• NM_001030019.2:c.232T>C

Variant summary

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

The NM_001030019.2(SUN3):​c.232T>C​(p.Ser78Pro) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SUN3 NM_001030019.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.138
• Publications: 0 publications found

Genes affected

SUN3 (HGNC:22429): (Sad1 and UNC84 domain containing 3) Predicted to enable protein-membrane adaptor activity. Predicted to be involved in nuclear envelope organization. Predicted to be integral component of nuclear inner membrane. Predicted to be part of meiotic nuclear membrane microtubule tethering complex. Predicted to be active in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

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 (MetaRNN=0.06266791).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001030019.2. 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
	SUN3	NM_001030019.2	MANE Select	c.232T>C	p.Ser78Pro	missense	Exon 3 of 10	NP_001025190.1	Q8TAQ9-1
	SUN3	NM_152782.4		c.232T>C	p.Ser78Pro	missense	Exon 4 of 11	NP_689995.3
	SUN3	NM_001284350.2		c.196T>C	p.Ser66Pro	missense	Exon 4 of 11	NP_001271279.1	Q8TAQ9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN3	ENST00000297325.9	TSL:5 MANE Select	c.232T>C	p.Ser78Pro	missense	Exon 3 of 10	ENSP00000297325.4	Q8TAQ9-1
	SUN3	ENST00000395572.6	TSL:1	c.232T>C	p.Ser78Pro	missense	Exon 4 of 11	ENSP00000378939.2	Q8TAQ9-1
	SUN3	ENST00000412142.5	TSL:5	c.196T>C	p.Ser66Pro	missense	Exon 5 of 12	ENSP00000410204.2	Q8TAQ9-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

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	Benign	0.065
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.1
DANN	Benign	0.95
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.14
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.0080
Sift	Benign	0.26	T
Sift4G	Benign	0.18	T
Polyphen		0.0010	B
Vest4		0.23
MutPred		0.36		Gain of loop (P = 0.0166)
MVP		0.16
MPC		0.082
ClinPred		0.053	T
GERP RS		-0.27
PromoterAI		0.0018	Neutral
Varity_R		0.12
gMVP		0.16
Mutation Taster		=96/4	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

hg19: chr7-48056915;