7-47996133-A-C

Position:

• chr7-47996133-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001030019.2(SUN3):​c.591T>G​(p.Ile197Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000704 in 1,420,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SUN3 NM_001030019.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.89

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29980338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUN3	NM_001030019.2	c.591T>G	p.Ile197Met	missense_variant	7/10	ENST00000297325.9	NP_001025190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUN3	ENST00000297325.9	c.591T>G	p.Ile197Met	missense_variant	7/10	5	NM_001030019.2	ENSP00000297325	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1420008 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 706938

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.17e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2024

The c.591T>G (p.I197M) alteration is located in exon 7 (coding exon 7) of the SUN3 gene. This alteration results from a T to G substitution at nucleotide position 591, causing the isoleucine (I) at amino acid position 197 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T;.;.;T;.;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	.;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.30	T;T;T;T;T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.8	M;.;.;M;.;.
MutationTaster	Benign	0.92	D;D;D;D;D
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.6	N;N;.;N;N;.
REVEL	Benign	0.14
Sift	Uncertain	0.021	D;D;.;D;D;.
Sift4G	Uncertain	0.012	D;D;D;D;D;D
Polyphen		0.97	D;.;.;D;P;.
Vest4		0.37
MutPred		0.36		Gain of disorder (P = 0.0597);.;.;Gain of disorder (P = 0.0597);.;.;
MVP		0.61
MPC		0.29
ClinPred		0.93	D
GERP RS		4.1
Varity_R		0.099
gMVP		0.36

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-48035730;