chr4-2239007-T-G

Variant names:

• chr4-2239007-T-G
• rs143565122
• NM_001303143.2:c.946A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001303143.2(HAUS3):​c.946A>C​(p.Ser316Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,392,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HAUS3 NM_001303143.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.458

Genes affected

HAUS3 (HGNC:28719): (HAUS augmin like complex subunit 3) This gene encodes a component of the HAUS augmin-like protein complex, which plays a key role in cytokinesis and mitosis. Disruption of the encoded protein causes mitotic defects resulting from fragmentation of centrosomes and microtubule destabilization. This gene shares its 5' exons with some transcripts from overlapping GeneID: 353497, which encodes a DNA polymerase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

POLN (HGNC:18870): (DNA polymerase nu) This gene encodes a DNA polymerase type-A family member. The encoded protein plays a role in DNA repair and homologous recombination. This gene shares its 5' exons with some transcripts from overlapping GeneID: 79441, which encodes an augmentin-like protein complex subunit. [provided by RefSeq, Dec 2014]

ENSG00000290263 (HGNC:):

COX6B1P5 (HGNC:37675): (cytochrome c oxidase subunit 6B1 pseudogene 5)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.119939655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAUS3	NM_001303143.2	c.946A>C	p.Ser316Arg	missense_variant	Exon 4 of 6	ENST00000443786.3	NP_001290072.1
POLN	NM_181808.4	c.-13+2513A>C		intron_variant	Intron 2 of 25	ENST00000511885.6	NP_861524.2
HAUS3	NM_024511.7	c.946A>C	p.Ser316Arg	missense_variant	Exon 3 of 5		NP_078787.2
COX6B1P5		n.2239007T>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAUS3	ENST00000443786.3	c.946A>C	p.Ser316Arg	missense_variant	Exon 4 of 6	1	NM_001303143.2	ENSP00000392903.2
POLN	ENST00000511885.6	c.-13+2513A>C		intron_variant	Intron 2 of 25	5	NM_181808.4	ENSP00000435506.1
ENSG00000290263	ENST00000672725.1	n.946A>C		non_coding_transcript_exon_variant	Exon 3 of 19			ENSP00000500518.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1392702 Hom.: 0 Cov.: 30 AF XY: 0.00000291 AC XY: 2 AN XY: 688074

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: 0.0000269

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.10	.;T;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.66	T;.;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.3	L;L;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.055
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.32	T;T;T
Polyphen		0.0010	.;B;B
Vest4		0.33
MutPred		0.22		Gain of MoRF binding (P = 0.0087);Gain of MoRF binding (P = 0.0087);Gain of MoRF binding (P = 0.0087);
MVP		0.27
MPC		0.019
ClinPred		0.043	T
GERP RS		-0.23
Varity_R		0.13
gMVP		0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs143565122; hg19: chr4-2240734;